Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 544
Filter
1.
Ann Intern Med ; 175(11): 1617-1618, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2203122
2.
Nutrients ; 14(21)2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2200560

ABSTRACT

ß-Hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older adults. Therefore, we tested the hypothesis that combining HMB plus Vitamin D3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women.


Subject(s)
Cholecalciferol , Muscle Strength , Humans , Middle Aged , Female , Aged , Cholecalciferol/pharmacology , Dietary Supplements , Muscle, Skeletal , Double-Blind Method
3.
Mult Scler Relat Disord ; 66: 104025, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2181739

ABSTRACT

BACKGROUND: This analysis evaluated long-term safety findings from the SAkuraSky and SAkuraStar studies with satralizumab in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: SAkuraSky (satralizumab in combination with baseline immunosuppressive therapy; IST) and SAkuraStar (satralizumab monotherapy) are international, multicenter, randomized, placebo-controlled, phase 3 studies consisting of a double-blind (DB) period followed by an open-label extension (OLE). The overall satralizumab treatment (OST) period safety population comprised patients receiving ≥1 dose of satralizumab in the DB and/or OLE periods (cut-off date: 22 February 2021). Safety was evaluated in the DB and OST periods. RESULTS: In the SAkuraSky DB period, patients received satralizumab (n = 41) or placebo (n = 42) in addition to stable baseline IST; 75 patients were included in the OST population. In the SAkuraStar DB period, 63 patients received satralizumab monotherapy and 32 received placebo; 91 patients were included in the OST population. Median treatment exposure in the OST period was 4.4 years (range 0.1-7.0) in SAkuraSky and 4.0 years (range 0.1-6.1) in SAkuraStar. Rates of adverse events (AEs per 100 patient-years) and serious AEs in the OST period were comparable with satralizumab and placebo in the DB periods of both studies. Similarly, overall rates of infections and serious infections were consistent between the OST and DB periods with satralizumab, with no increase in rates of infections or serious infections over time. In the OST periods, longer exposure to satralizumab was not associated with a higher risk of severe (grade ≥3) laboratory changes versus the DB periods. No deaths or anaphylactic reactions to treatment with satralizumab were reported during the OST periods of both studies. CONCLUSION: The safety profile of satralizumab as a monotherapy or in combination with IST was maintained in the OLE, and no new safety concerns versus the DB period were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02028884 (SAkuraSky) and NCT02073279 (SAkuraStar).


Subject(s)
Antibodies, Monoclonal, Humanized , Neuromyelitis Optica , Humans , Double-Blind Method , Neuromyelitis Optica/drug therapy , Antibodies, Monoclonal, Humanized/adverse effects
4.
Circ Heart Fail ; 14(3): e007767, 2021 03.
Article in English | MEDLINE | ID: covidwho-2153215

ABSTRACT

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


Subject(s)
Canagliflozin/therapeutic use , Heart Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Telemedicine , Actigraphy/instrumentation , Canagliflozin/adverse effects , Double-Blind Method , Exercise Tolerance/drug effects , Fitness Trackers , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Mobile Applications , Quality of Life , Randomized Controlled Trials as Topic , Recovery of Function , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Stroke Volume/drug effects , Telemedicine/instrumentation , Time Factors , Treatment Outcome , United States , Ventricular Function, Left/drug effects
5.
Brain Stimul ; 15(3): 761-768, 2022.
Article in English | MEDLINE | ID: covidwho-2130191

ABSTRACT

BACKGROUND: Both activated by environmental odorants, there is a clear role for the intranasal trigeminal and olfactory nerves in smell function. Unfortunately, our ability to perceive odorants decreases with age or with injury, and limited interventions are available to treat smell loss. OBJECTIVE: We investigated whether electrical stimulation of the trigeminal nerve via trigeminal nerve stimulation (TNS) or transcranial direct current stimulation (tDCS) modulates odor sensitivity in healthy individuals. METHODS: We recruited 20 healthy adults (12 Female, mean age = 27) to participate in this three-visit, randomized, double-blind, sham-controlled trial. Participants were randomized to receive one of three stimulation modalities (TNS, tDCS, or sham) during each of their visits. Odor detection thresholds were obtained at baseline, immediately post-intervention, and 30-min post-intervention. Furthermore, participants were asked to complete a sustained attention task and mood assessments before odor detection testing. RESULTS: Findings reveal a timeXcondition interaction for guaiacol (GUA) odorant detection thresholds (F (3.188, 60.57) = 3.833, P = 0.0125), but not phenyl ethyl alcohol (PEA) odorant thresholds. At 30-min post-stimulation, both active TNS and active tDCS showed significantly increased sensitivity to GUA compared to sham TNS (Sham TNS = -8.30% vs. Active TNS = 9.11%, mean difference 17.43%, 95% CI 5.674 to 29.18, p = 0.0044; Sham TNS = -8.30% vs. Active tDCS = 13.58%, mean difference 21.89%, 95% CI 10.47 to 33.32, p = 0.0004). CONCLUSION: TNS is a safe, simple, noninvasive method for boosting olfaction. Future studies should investigate the use of TNS on smell function across different stimulation parameters, odorants, and patient populations.


Subject(s)
Smell , Transcranial Direct Current Stimulation , Adult , Double-Blind Method , Electric Stimulation , Female , Humans , Transcranial Direct Current Stimulation/methods , Trigeminal Nerve/physiology
6.
Lancet Respir Med ; 10(2): 167-179, 2022 02.
Article in English | MEDLINE | ID: covidwho-2115380

ABSTRACT

BACKGROUND: The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. METHODS: We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria-with no contraindications to influenza vaccination-were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 µg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18-64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. FINDINGS: Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to <65 years) was 87·5% (95% CI -0·2 to 98·4) and in the main study was 89·8% (95% CI 79·7-95·5). INTERPRETATION: To our knowledge, this substudy is the first to show the safety, immunogenicity, and efficacy profile of a COVID-19 vaccine when co-administered with seasonal influenza vaccines. Our results suggest concomitant vaccination might be a viable immunisation strategy. FUNDING: Novavax.


Subject(s)
COVID-19 , Influenza Vaccines , Adolescent , Adult , Aged , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine , Influenza Vaccines/adverse effects , Middle Aged , SARS-CoV-2 , Seasons , Young Adult
7.
Lancet ; 399(10342): 2212-2225, 2022 06 11.
Article in English | MEDLINE | ID: covidwho-2114721

ABSTRACT

BACKGROUND: Vaccination of children and young people against SARS-CoV-2 is recommended in some countries. Scarce data have been published on immune responses induced by COVID-19 vaccines in people younger than 18 years compared with the same data that are available in adults. METHODS: COV006 is a phase 2, single-blind, randomised, controlled trial of ChAdOx1 nCoV-19 (AZD1222) in children and adolescents at four trial sites in the UK. Healthy participants aged 6-17 years, who did not have a history of chronic respiratory conditions, laboratory-confirmed COVID-19, or previously received capsular group B meningococcal vaccine (the control), were randomly assigned to four groups (4:1:4:1) to receive two intramuscular doses of 5 × 1010 viral particles of ChAdOx1 nCoV-19 or control, 28 days or 84 days apart. Participants, clinical investigators, and the laboratory team were masked to treatment allocation. Study groups were stratified by age, and participants aged 12-17 years were enrolled before those aged 6-11 years. Due to the restrictions in the use of ChAdOx1 nCoV-19 in people younger than 30 years that were introduced during the study, only participants aged 12-17 years who were randomly assigned to the 28-day interval group had received their vaccinations at the intended interval (day 28). The remaining participants received their second dose at day 112. The primary outcome was assessment of safety and tolerability in the safety population, which included all participants who received at least one dose of the study drug. The secondary outcome was immunogenicity, which was assessed in participants who were seronegative to the nucleocapsid protein at baseline and received both prime and boost vaccine. This study is registered with ISRCTN (15638344). FINDINGS: Between Feb 15 and April 2, 2021, 262 participants (150 [57%] participants aged 12-17 years and 112 [43%] aged 6-11 years; due to the change in the UK vaccination policy, the study terminated recruitment of the younger age group before the planned number of participants had been enrolled) were randomly assigned to receive vaccination with two doses of either ChAdOx1 nCoV-19 (n=211 [n=105 at day 28 and n=106 at day 84]) or control (n=51 [n=26 at day 28 and n=25 at day 84]). One participant in the ChAdOx1 nCoV-19 day 28 group in the younger age bracket withdrew their consent before receiving a first dose. Of the participants who received ChAdOx1 nCoV-19, 169 (80%) of 210 participants reported at least one solicited local or systemic adverse event up to 7 days following the first dose, and 146 (76%) of 193 participants following the second dose. No serious adverse events related to ChAdOx1 nCoV-19 administration were recorded by the data cutoff date on Oct 28, 2021. Of the participants who received at least one dose of ChAdOx1 nCoV-19, there were 128 unsolicited adverse events up to 28 days after vaccination reported by 83 (40%) of 210 participants. One participant aged 6-11 years receiving ChAdOx1 nCoV-19 reported a grade 4 fever of 40·2°C on day 1 following first vaccination, which resolved within 24 h. Pain and tenderness were the most common local solicited adverse events for all the ChAdOx1 nCoV-19 and capsular group B meningococcal groups following both doses. Of the 242 participants with available serostatus data, 14 (6%) were seropositive at baseline. Serostatus data were not available for 20 (8%) of 262 participants. Among seronegative participants who received ChAdOx1 nCoV-19, anti-SARS-CoV-2 IgG and pseudoneutralising antibody titres at day 28 after the second dose were higher in participants aged 12-17 years with a longer interval between doses (geometric means of 73 371 arbitrary units [AU]/mL [95% CI 58 685-91 733] and 299 half-maximal inhibitory concentration [IC50; 95% CI 230-390]) compared with those aged 12-17 years who received their vaccines 28 days apart (43 280 AU/mL [95% CI 35 852-52 246] and 150 IC50 [95% CI 116-194]). Humoral responses were higher in those aged 6-11 years than in those aged 12-17 years receiving their second dose at the same 112-day interval (geometric mean ratios 1·48 [95% CI 1·07-2·07] for anti-SARS-CoV-2 IgG and 2·96 [1·89-4·62] for pseudoneutralising antibody titres). Cellular responses peaked after a first dose of ChAdOx1 nCoV-19 across all age and interval groups and remained above baseline after a second vaccination. INTERPRETATION: ChAdOx1 nCoV-19 is well tolerated and immunogenic in children aged 6-17 years, inducing concentrations of antibody that are similar to those associated with high efficacy in phase 3 studies in adults. No safety concerns were raised in this trial. FUNDING: AstraZeneca and the UK Department of Health and Social Care through the UK National Institute for Health and Care Research.


Subject(s)
COVID-19 , Meningococcal Vaccines , Adolescent , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Child , Double-Blind Method , Humans , Immunoglobulin G , SARS-CoV-2 , Single-Blind Method
8.
Ann Intern Med ; 175(10): JC115, 2022 10.
Article in English | MEDLINE | ID: covidwho-2110760

ABSTRACT

SOURCE CITATION: Wolfe CR, Tomashek KM, Patterson TF, et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. Lancet Respir Med. 2022;10:888-99. 35617986.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Azetidines , COVID-19/drug therapy , Dexamethasone/therapeutic use , Double-Blind Method , Humans , Purines , Pyrazoles , Sulfonamides
9.
Nat Commun ; 13(1): 6952, 2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2119472

ABSTRACT

Data on safety and immunity elicited by a third booster dose of inactivated COVID-19 vaccine in children and adolescents are scarce. Here we conducted a study based on a double-blind, randomised, placebo-controlled phase 2 clinical trial (NCT04551547) to assess the safety and immunogenicity of a third dose of CoronaVac. In this study, 384 participants in the vaccine group were assigned to two cohorts. One received the third dose at a 10-months interval (cohort 1) and the other one at a 12-months interval (cohort 2). The primary endpoint is safety and immunogenicity following a third dose of CoronaVac. The secondary endpoint is antibody persistence following the primary two-dose schedule. Severities of local and systemic adverse reactions reported within 28 days after dose 3 were mild and moderate in both cohorts. A third dose of CoronaVac increased GMTs to 681.0 (95%CI: 545.2-850.7) in cohort 1 and 745.2 (95%CI: 577.0-962.3) in cohort 2. Seropositivity rates against the prototype were 100% on day 28 after dose 3. Seropositivity rates against the Omicron variant were 90.6% (cohort 1) and 91.5% (cohort 2). A homologous booster dose of CoronaVac is safe and induces a significant neutralising antibody levels increase in children and adolescents.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Adolescent , Child , SARS-CoV-2 , COVID-19/prevention & control , Antibodies, Neutralizing , Double-Blind Method , Antibodies, Viral
10.
J Alzheimers Dis ; 90(2): 811-822, 2022.
Article in English | MEDLINE | ID: covidwho-2109698

ABSTRACT

BACKGROUND: Recent innovative non-pharmacological interventions and neurostimulation devices have shown potential for application in the treatment of Alzheimer's disease (AD). These include photobiomodulation (PBM) therapy. OBJECTIVE: This pilot study assesses the safety, compliance with, and efficacy of a brain-gut PBM therapy for mild-to-moderate AD patients. METHODS: This double-blind, randomized, monocentric sham-controlled study started in 2018 and ended prematurely in 2020 due to the COVID-19 pandemic. Fifty-three mild-to-moderate AD patients were randomized, 27 in the PBM group and 26 in the sham group. All patients had 40 treatment sessions lasting 25 min each over 8 weeks and were followed for 4 weeks afterwards. Compliance with the treatment was recorded. Safety was assessed by recording adverse events (AEs), and efficacy was evaluated using neuropsychological tests. RESULTS: The PBM therapy proved to be safe in regard to the number of recorded AEs (44% of the patients), which were balanced between the PBM and sham groups. AEs were mainly mild, and no serious AEs were reported. The majority of the patients (92.5%) were highly compliant, which confirms the feasibility of the PBM treatment. Compared to the sham patients, the PBM patients showed lower ADAS-Cog comprehension subscores, higher forward verbal spans, and lower TMT-B execution times, which suggests an improvement in cognitive functions. CONCLUSION: This study demonstrates the tolerability of and patient compliance with a PBM-based treatment for mild-to-moderate AD patients. It highlights encouraging efficacy trends and provides insights for the design of the next phase trial in a larger AD patient sample.


Subject(s)
Alzheimer Disease , COVID-19 , Low-Level Light Therapy , Humans , Pilot Projects , Pandemics , Treatment Outcome , Alzheimer Disease/radiotherapy , Alzheimer Disease/drug therapy , Brain , Double-Blind Method , Patient Compliance
11.
J Transl Med ; 20(1): 506, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2108800

ABSTRACT

BACKGROUND: Many patients who recovered from COVID are still suffering from pulmonary dysfunction that can be persistent even for months after infection. Therefore, treatment to prevent irreversible impairment of lung function is needed. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory and antifibrotic effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae. METHODS: The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history (with the first symptoms of COVID appear no earlier than 2 months before screening) and having fibrotic changes in the lungs, decreased lung function (percentage of predicted FVC and/or DLCO < 80%), and moderate or severe dyspnea according to mMRC scale were enrolled and randomly assigned in a 1:1 ratio (stratified by the initial degree of lung damage, age, and concomitant chronic diseases) by use of interactive responsive technology to peroral administration of Treamid 50 mg or placebo once a day for 4 weeks. The primary outcome was the proportion of patients who achieved clinically significant improvement in FVC and/or DLCO (defined as a relative increase in FVC of ≥ 10% or a relative increase in FVC in the range of ≥ 5 to < 10% plus a relative increase in DLCO of ≥ 15%) at week 4 compared with baseline. Secondary endpoints included changes from baseline in dyspnea scoring evaluated by the modified Borg and mMRC scales, pulmonary function (FEV1, FVC, FEV1/FVC ratio, DLCO, TLC, FRC), 6-min walk distance, the overall score of the KBILD questionnaire, and the proportion of patients with a reduction in the degree of lung damage assessed by CT scores. This trial was registered on ClinicalTrials.gov (Identifier: NCT04527354). The study was fully funded by PHARMENTERPRISES LLC. RESULTS: 12 out of 29 patients (41%) in Treamid group achieved clinically significant improvement in FVC and/or DLCO compared to 5 out of 30 patients (17%) in placebo group (p = 0.036). There was a significant decrease of dyspnea according to modified Borg scale observed in the Treamid group (- 0.9 ± 0.7 vs. - 0.4 ± 0.8, p = 0.018). No significant differences in the adverse events were noted. Exploratory analysis of the female population indicated superiority of Treamid over placebo by decreasing dyspnea and the extent of lung damage as well as increasing TLC. CONCLUSIONS: 4 weeks oral administration of 50 mg Treamid was associated with clinically significant improvement in the post-COVID patients, evident by an increase in FVC and/or DLCO as well as decreasing dyspnea. Treamid was well tolerated and can be safely administered to patients discharged after COVID. Treamid was more effective in women visible by superior improvement of COVID sequalae after 4 weeks treatment. Considering that female gender is a risk factor associated with the development of post-COVID symptoms, Treamid might offer a pharmacological treatment for long-term sequalae after COVID and supports further investigation in future clinical trials in post-COVID patients.


Subject(s)
COVID-19 , Female , Humans , COVID-19/complications , COVID-19/drug therapy , Lung , Double-Blind Method , Respiratory Function Tests , Dyspnea , Treatment Outcome
12.
Sci Rep ; 12(1): 18604, 2022 Nov 03.
Article in English | MEDLINE | ID: covidwho-2106462

ABSTRACT

Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.


Subject(s)
COVID-19 , Cholecalciferol , Humans , Cholecalciferol/therapeutic use , Vitamin D/therapeutic use , Intensive Care Units , Double-Blind Method , Dietary Supplements , Immunity, Cellular
13.
Psychopharmacol Bull ; 52(4): 8-30, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2101824

ABSTRACT

Objective: In a phase 2 study, pimavanserin demonstrated efficacy as adjunctive treatment for major depressive disorder (MDD). Subsequently, two phase 3 studies (NCT03968159 in the US; NCT03999918 in Europe) were initiated to examine the efficacy and safety of adjunctive pimavanserin in subjects with MDD and inadequate response to antidepressant treatment. Studies were combined with a prespecified statistical analysis plan owing to recruitment challenges related to the COVID-19 pandemic. Experimental design: The randomized, double-blind studies enrolled 298 patients with MDD and inadequate response to current antidepressants. Patients were randomly assigned 1:1 to pimavanserin or placebo added to current antidepressant for 6 weeks. Primary endpoint was change from baseline to week 5 in the Hamilton Rating Scale for Depression, 17-item version (HAM-D-17). Principal observations: There was no effect of pimavanserin in change from baseline to week 5 in the HAM-D-17 (pimavanserin [n = 138]: least-squares mean [LSM] [standard error {SE}], -9.0 [0.58]; placebo [n = 135]: -8.1 [0.58]; mixed-effects model for repeated measures LSM [SE] difference, -0.9 [0.82], P = 0.2956). Nominal improvement with pimavanserin was observed on 2 secondary endpoints: Clinical Global Impressions-Severity scale, Karolinska Sleepiness Scale. Treatment-emergent adverse events occurred in 58.1% of pimavanserin-treated and 54.7% of placebo-treated patients. Conclusions: Adjunctive pimavanserin did not significantly improve depressive symptoms, although pimavanserin was well tolerated.


Subject(s)
COVID-19 , Depressive Disorder, Major , Humans , Depressive Disorder, Major/drug therapy , Double-Blind Method , Pandemics , Antidepressive Agents/adverse effects , Treatment Outcome
14.
BMJ Open ; 12(11): e061870, 2022 11 02.
Article in English | MEDLINE | ID: covidwho-2097985

ABSTRACT

INTRODUCTION: Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL. METHODS AND ANALYSIS: A randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board. ETHICS AND DISSEMINATION: The trial is approved by the Swedish National Institutional Review Board (2021-02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access. TRIAL REGISTRATION NUMBER: NCT04842448.


Subject(s)
COVID-19 , Hyperbaric Oxygenation , Humans , Clinical Trials, Phase II as Topic , COVID-19/therapy , Double-Blind Method , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
15.
Vaccine ; 40(49): 7130-7140, 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2096111

ABSTRACT

BACKGROUND: After establishing safety and immunogenicity of Biological-E's CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study. METHODS: This is a phase-2/3 prospective, randomised, double-blind, placebo-controlled study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents of either gender between <18 to ≥12 years of age in Phase-2 and <18 to ≥5 years of age in Phase-Phase-2/Phase-3 with placebo as a control. This study has two age sub-groups; subgroup-1 with subjects <18 to ≥12 years of age and subgroup-2 with subjects <12 to ≥5 years of age. In both sub groups, eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX™ vaccine or Placebo in 3:1 ratio. FINDINGS: The safety profile of CORBEVAX™ vaccine in both pediatric cohorts was comparable to the placebo-control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious-AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX™ vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing-antibody (nAb)-titers against Ancestral-Wuhan and Delta-strains. Significantly high interferon-gamma immune- response (cellular) was elicited by CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion. INTERPRETATIONS: The safety profile of CORBEVAX™ vaccine in <18 to ≥5 years' children and adolescents was found to be safe and tolerable. Significant increase in anti-RBD-IgG and nAb-titers and IFN-gamma immune-responses were observed post-vaccination in both pediatric age sub-groups. The nAb titers observed in both the pediatric age cohorts were non-inferior to the adult cohort (BECT069 study) in terms of ratio of the GMT's of both the cohorts. This study shows that CORBEVAX™ vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old. The study was prospectively registered with clinical trial registry of India- CTRI/2021/10/037066.


Subject(s)
COVID-19 , Vaccines , Adult , Humans , Child , Adolescent , Child, Preschool , SARS-CoV-2 , Prospective Studies , COVID-19/prevention & control , Double-Blind Method , Immunoglobulin G , Immunogenicity, Vaccine , Antibodies, Viral , Antibodies, Neutralizing
16.
JAMA ; 328(16): 1595-1603, 2022 10 25.
Article in English | MEDLINE | ID: covidwho-2084929

ABSTRACT

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.


Subject(s)
Anti-Infective Agents , COVID-19 , Hospitalization , Ivermectin , Female , Humans , Middle Aged , COVID-19/drug therapy , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines/therapeutic use , Double-Blind Method , Ivermectin/adverse effects , Ivermectin/therapeutic use , SARS-CoV-2 , Treatment Outcome , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Ambulatory Care , Drug Repositioning , Time Factors , Recovery of Function , Male , Adult
17.
N Engl J Med ; 387(18): 1673-1687, 2022 11 03.
Article in English | MEDLINE | ID: covidwho-2077202

ABSTRACT

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).


Subject(s)
2019-nCoV Vaccine mRNA-1273 , COVID-19 , Immunogenicity, Vaccine , Child , Child, Preschool , Humans , Infant , Young Adult , 2019-nCoV Vaccine mRNA-1273/immunology , 2019-nCoV Vaccine mRNA-1273/therapeutic use , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Immunogenicity, Vaccine/immunology , Vaccine Efficacy , Treatment Outcome , Adolescent , Adult
19.
BMC Med ; 20(1): 342, 2022 09 27.
Article in English | MEDLINE | ID: covidwho-2053903

ABSTRACT

BACKGROUND: In vitro drug screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). METHODS: This was a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were enrolled, randomized, and allocated to each group using an interactive web response system. Randomization was performed using a minimization method with the factors medical institution, age, and underlying diseases (chronic respiratory disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular diseases, and obesity). The patients, investigators/subinvestigators, study coordinators, and other study personnel were blinded throughout the study. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. RESULTS: One-hundred fifty-five patients were randomized to receive camostat mesilate (n = 78) or placebo (n = 77). The median time to the first test was 11.0 days (95% confidence interval [CI]: 9.0-12.0) in the camostat mesilate group and 11.0 days (95% CI: 10.0-13.0) in the placebo group. Conversion to negative viral status by day 14 was observed in 45 of 74 patients (60.8%) in the camostat mesilate group and 47 of 74 patients (63.5%) in the placebo group. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. CONCLUSIONS: Camostat mesilate did not substantially reduce the time to viral clearance, based on upper airway viral loads, compared with placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04657497. Japan Registry for Clinical Trials, jRCT2031200198.


Subject(s)
COVID-19 , Bayes Theorem , COVID-19/drug therapy , Double-Blind Method , Esters/adverse effects , Esters/therapeutic use , Guanidines/adverse effects , Guanidines/therapeutic use , Humans , SARS-CoV-2 , Treatment Outcome
20.
Int J Environ Res Public Health ; 19(18)2022 Sep 19.
Article in English | MEDLINE | ID: covidwho-2043691

ABSTRACT

The current study investigated the impact of different doses of Nigella sativa seeds on the symptoms, the cluster of differentiation profile group, and inflammatory markers of mild COVID-19 cases. METHODS: The study was a double-blind placebo-controlled clinical trial. Patients with mild and asymptomatic SARS-CoV-2 infection patients were randomly subdivided into seven subgroups: Group (GP) 1: received charcoal capsules as a control group, and GP 2: received three capsules of whole Nigella sativa seeds daily, two capsules in the morning and one in the evening; GP 3: received three capsules of whole Nigella sativa seeds every 12 h, GP 4: received five capsules in the morning and four capsules of whole Nigella sativa seeds in the evening, GP 5: received one capsule of Nigella sativa powder every 12 h; GP 6: received two capsules of Nigella sativa powder every 12 h; GP 7: received three capsules of Nigella sativa powder every 12 h; all treatment course was for ten days. Inflammatory parameters were assessed before and after interventions. RESULTS: 262 subjects were included in the final analysis. No significant difference was detected regarding age, gender, and nationality. No significant differences were detected between the inflammatory marker in all groups. The WBCs showed a significant difference between before and after the intervention. While for procalcitonin, a significant difference was demonstrated in groups 1,4, and 6. CONCLUSIONS: The current randomized clinical trial did not reveal a significant effect of ten days of treatment with various doses of Nigella sativa on symptoms, differentiation profile, and inflammatory markers of patients with COVID-19. As a natural product, the effect of Nigella sativa on disease requires weeks to manifest itself.


Subject(s)
Biological Products , COVID-19 , Nigella sativa , COVID-19/drug therapy , Charcoal , Double-Blind Method , Humans , Phytotherapy , Powders , Procalcitonin , SARS-CoV-2 , Seeds
SELECTION OF CITATIONS
SEARCH DETAIL