Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients.

In COVID-19 patients, cytokine storm due to excessive immune responses can cause severe complications. In this study, we investigated the effect of curcumin nanomicelles on clinical outcome and cellular immune responses subtypes changes in COVID-19 patients. A randomized, triple-blinded, placebo-controlled study was done. Forty COVID-19 patients were included into two groups of nano-curcumin and placebo. The nano-curcumin group received 40 mg of nano-curcumin capsule, four times per day for 2 weeks. Clinical signs and gene expression of TBX21, GATA3, RORC and FOXP3 genes and IFN-γ, IL-4, IL-17 and TGF-ß cytokines serum levels were measured at time points of 0, 7 and 14 days. Serum levels of IFN-γ (p = .52) and IL-17 (p = .11) decreased, while IL-4 (p = .12) and TGF-ß (p = .14) increased in the nano-curcumin group compared with placebo on day 14. Moreover, gene expressions of TBX21 (p = .02) and FOXP3 (p = .005) genes were significantly decreased and increased between nano-curcumin and placebo groups on day 7, respectively. It can be concluded that administration of nano-curcumin in inflammatory phase of COVID-19 can accelerate recovering of the acute inflammatory phase by modulating inflammatory immune responses. Therefore, it is suggested that this supplement in inflammatory diseases, including COVID-19, can be effective in controlling the inflammatory responses.

Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial.

BACKGROUND: Curcumin, a natural polyphenolic compound, is proposed as a potential treatment option for patients with coronavirus disease by inhibiting the entry of virus to the cell, encapsulation of the virus and viral protease, as well as modulating various cellular signaling pathways. In this study, the efficacy and safety of nanocurcumin oral formulation has been evaluated in patients with mild-moderate Coronavirus disease 2019 (COVID-19) in outpatient setting. METHODS: In this triple-blind randomized placebo-controlled clinical trial, sixty mild to moderate COVID-19 patients in outpatient setting who fulfilled the inclusion criteria were randomly allocated to treatment (n = 30) group to receive oral nanocurcumin formulation (Sinacurcumin soft gel which contains 40 mg curcuminoids as nanomicelles), two soft gels twice a day after food for 2 weeks or placebo (n = 30) group. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period and compared between two groups. RESULTS: All symptoms except sore throat resolved faster in the treatment group and the difference was significant for chills, cough and smell and taste disturbances. The CRP serum level was lower in the treatment group at the end of two weeks and the lymphocyte count was significantly higher in treatment group. No significant adverse reaction reported in the treatment group. CONCLUSION: Oral nanoformulation of curcumin can significantly improve recovery time in patients with mild to moderate COVID-19 in outpatient setting. Further studies with larger sample size are recommended.

Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial.

Curcumin is proposed as a potential treatment option for coronavirus disease-19 (COVID-19) by inhibiting the virus entrance, encapsulation and replication, and modulating various cellular signaling pathways. In this open-label nonrandomized clinical trial, efficacy of nano-curcumin oral formulation has been evaluated in hospitalized patients with mild-moderate COVID-19. Forty-one patients who fulfilled the inclusion criteria were allocated to nano-curcumin (n = 21) group (Sinacurcumin soft gel, contains 40 mg curcuminoids as nanomicelles, two capsules twice a day) or control (n = 20) group, for 2 weeks. Patients' symptoms and laboratory data were assessed at baseline and during follow-up period. Most of symptoms including fever and chills, tachypnea, myalgia, and cough resolved significantly faster in curcumin group. Moreover, SaO2 was significantly higher in treatment group after 2, 4, 7, and 14 days of follow-up and lymphocyte count after 7 and 14 days. Duration of supplemental O2 use and hospitalization was also meaningfully shorter in treatment group. It is also noteworthy to mention that no patient in treatment group experienced deterioration of infection during follow-up period, but it occurred in 40% of control group. Oral curcumin nano-formulation can significantly improve recovery time in hospitalized COVID-19 patients. Further randomized placebo controlled trials with larger sample size are recommended.

The clinical effect of Nano micelles containing curcumin as a therapeutic supplement in patients with COVID-19 and the immune responses balance changes following treatment: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To investigates the effectiveness of curcumin-containing Nanomicelles as a therapeutic supplement in the treatment of patients with COVID-19 and its effect on immune responses balance changes following treatment. TRIAL DESIGN: This study is conducted as a prospective, placebo-controlled with parallel group, single-center randomized clinical trial on COVID-19 patients. PARTICIPANTS: Patients are selected from the COVID-19 ward of Shahid Mohammadi Hospital in Bandar Abbas, Iran. INCLUSION CRITERIA: 1. Real time PCR-approved positive COVID-19 test. 2. Both gender 3. Age between 18 and 75 years 4. Signing a written consent 5. Lack of participation in other clinical trials Exclusion criteria: 1. Pregnancy or lactation 2. Allergy to turmeric or curcumin 3. Smoking 4. Patient connected to the ventilator 5. SaO2 less than 90% or PaO2 less than 8 kPa 6. Having comorbidities (such as severe renal failure, Glomerular filtration rate less than 30 ml/min, liver failure, Congestive heart failure, or Chronic obstructive pulmonary disease) 7. History of gallstones 8. History of gastritis or active gastrointestinal ulcer INTERVENTION AND COMPARATOR: In addition to the routine standard treatments for COVID-19, in the intervention group, 40mg nanomicelles containing curcumin (SinaCurcumin Capsule, Exir Nano Sina Company, Iran), four times per day (after breakfast, lunch, dinner and before bedtime) and in the placebo group as the control group, capsules with the same appearance and characteristics (Placebo capsules, Exir Nano Sina Company, Iran) are prescribed for two weeks. MAIN OUTCOMES: The effectiveness of Nano micelles containing curcumin treatment will be evaluated as daily clinical examinations of patients in both groups and, on days 0, 7 and 14, complete clinical symptoms and laboratory findings including peripheral blood and serum parameters such as inflammatory markers will be measured and recorded. Moreover, in order to evaluate the balance of immune responses changes following treatments, serum level of IFN-γ, IL-17, Il-4 and TGF-ß serum cytokines will be measured in both groups at time points of 0, 7 and 14 days post treatment. Gene expression of t-bet, GATA-3, FoxP3 and ROR- γT will also be measured at mentioned time points to assess the shift of T helper1, T helper2, T regulatory and T helper 17 immune responses following treatment. RANDOMISATION: Randomized trials will be performed on 40 COVID-19 patients which will be randomized using encoded sealed boxes with computer generated random digits with 1:1 allocation ratio. In order to randomization, placebo and SinaCurcumin Capsules will be numbered first by computer generated random digits. SinaCurcumin and placebo will then be stored and numbered in sealed packages based on generated random numbers. Finally, according to the order in which patients enter the study, packages are given to patients based on their number. BLINDING (MASKING): The present study will be blind for all patients, physicians and nurses, laboratory technicians and statisticians. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 40 patients will be included in the study, 20 of them will be randomly assigned to the intervention group and 20 to the placebo group. TRIAL STATUS: This is Version 1.0 of protocol dated 21 May 2020. The recruitment was started June 24, 2020 and is expected to be completed by October 31, 2020. TRIAL REGISTRATION: This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20200611047735N1", https://www.irct.ir/trial/48843 . Dated: 19 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.