Randomized, double blind, placebo controlled, clinical trial to study co-administration of Ashwagandha on safety, immunogenicity, and protection with COVID-19 vaccine: A Study Protocol

IntroductionThe government of India has rolled out COVID-19 vaccine program for individuals who are 18 years of age and above and priority is being given to the elderly, and individuals with morbidity. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD) is most widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Ashwagandha and its potential as vaccine adjuvant. We plan to study co-administration of Ashwagandha with COVISHIELD vaccine on safety, immunogenicity and protection. Methods and analysisWe designed a prospective, randomized, double blind, parallel group, placebo controlled, two arm, exploratory study on healthy volunteers receiving the COVISHIELD vaccine. In addition to the two dose schedule of COVISHIELD vaccine as per national guidelines, participants will be administered 8gm Ashwagandha or placebo tablets respectively per day. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. Adverse event following immunization will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. Ethics and disseminationEthical approval was obtained through the Central and institutional Ethics Committees. Participant recruitment is expected to commence by August 2021. Results will be presented in conferences and published in preprint followed by peer-reviewed medical journals. Registration detailsClinical Trial Registry - India (CTRI) Registration Number: CTRI/2021/06/034496. Date of Registration June 30, 2021. Strengths and limitations of this studyO_LINovel study to demonstrate effect of coadministration of immune adjuvant and COVID-19 vaccine on safety and immunogenicity. C_LIO_LIRandomised placebo controlled 28 weeks study with 80 percent power to demonstrate role of putative natural immunomodulator to augment the protection and reduce breakthrough infections C_LIO_LIState of art immune assays to measure specific antibodies to SARS-CoV-2 to demonstrate both persistent and late upsurge in immune response C_LIO_LIDaily tracking of participants using a study specific designed mobile app C_LIO_LIAn interim analysis is planned to provide information on early immune response after first dose of vaccine C_LIO_LIParticipants may be reluctant to donate blood repeatedly for immune assays; compliance with the test drug may be a challenge; asymptomatic infections may be missed; the study is not measuring cellular immune response. C_LI

Coadministration of AYUSH 64 as an adjunct to Standard of Care in mild and moderate COVID-19: A randomised, controlled, multicentric clinical trial

ObjectivesTo compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19. DesignMulticentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration. SettingCOVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital Participants140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe. InterventionsTwo tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease. Main outcome measuresTime period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol Results140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported. ConclusionsAYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted. Trial registrationThe Clinical Trials Registry India Number CTRI/2020/06/025557 FundingCCRAS, Ministry of AYUSH, Government of India

Search of novel model for integrative medicine / 中国结合医学杂志

This article provides global and Indian scenario with strengths and limitations of present health care system. Affordability, accessibility and availability of health care coupled with disproportionate growth and double burden of diseases have become major concerns in India. This article emphasizes need for mindset change from illness-disease-drug centric curative to person-health-wellness centric preventive and promotive approaches. It highlights innovation deficit faced pharmaceutical industry and drugs being withdrawn from market for safety reasons. Medical pluralism is a growing trend and people are exploring various options including modern, traditional, complementary and alternative medicine. In such a situation, knowledge from Ayurveda, yoga, Chinese medicine and acupuncture may play an important role. We can evolve a suitable model by integrating modern and traditional systems of medicine for affordable health care. In the larger interest of global community, Indian and Chinese systems should share knowledge and experiences for mutual intellectual enrichments and work together to evolve a novel model of integrative medicine.

Plant-based Rasayana drugs from Ayurveda / 中国结合医学杂志

Rasayana tantra is one of the eight specialties of Ayurveda. It is a specialized practice in the form of rejuvenative recipes, dietary regimen, special health promoting behaviour and drugs. Properly administered Rasayana can bestow the human being with several benefits like longevity, memory, intelligence, freedom from diseases, youthful age, excellence of luster, complexion and voice, optimum strength of physique and sense organs, respectability and brilliance. Various types of plant based Rasayana recipes are mentioned in Ayurveda. Review of the current literature available on Rasayanas indicates that anti-oxidant and immunomodulation are the most studied activities of the Rasayana drugs. Querying in Pubmed database on Rasayanas reveals that single plants as well as poly herbal formulations have been researched on. This article reviews the basics of Rasayana therapy and the published research on different Rasayana drugs for specific health conditions. It also provides the possible directions for future research.

Development and application of RAPD-SCAR marker for identification of Phyllanthus emblica LINN.

Correct genotype identification of medicinal plant material remains important for botanical drug industry. Limitations of chemical and morphological approaches for authentication have generated need for newer methods in quality control of botanicals. The present study was carried out to develop DNA based marker for identification of Phyllanthus emblica LINN. A putative marker (1.1 kb) specific for P. emblica was identified by Random Amplified Polymorphic DNA (RAPD) technique. Sequence Characterized Amplified Region (SCAR) marker was developed from the RAPD amplicon. The SCAR marker was found useful for identification of P. emblica in its commercial samples and Triphalachurna, a multi-component Ayurvedic formulation.

Classification of human population based on HLA gene polymorphism and the concept of Prakriti in Ayurveda.

BACKGROUND: Correlating phenotypes with genotypes remains the major postgenomic challenge. Attempts to correlate phenotype characteristics associated with ethnicity, geographical divisions, or diseases to genotypes have had limited success. This means that current approaches for identifying phenotypes associated with haplotypes may be inadequate. OBJECTIVES: We hypothesize that a human phenome based on Ayurveda could provide an appropriate approach. Specifically, there could be a genetic basis for the three major constitutions (Prakriti) described in Ayurveda. The Prakriti classification is based on differences in physical, physiological, and psychologics characteristics and is independent of racial, ethnic, or geographical considerations. It may provide an appropriate means of classifying phenotypes to be considered collectively for genotyping. DESIGN: As a pilot study to test the hypothesis, we evaluated 76 subjects both for their Prakriti and human leucocyte antigen (HLA) DRB1 types. The genomic DNA was extracted using a standard protocol. Subsequently, HLA DRB1 typing was done by low-resolution polymerase chain reaction sequence specific primers and oligonucleotide probes. RESULTS: We observed a reasonable correlation between HLA type and Prakriti type. The complete absence of the HLA DRB1*02 allele in the Vata type and of HLA DRB1*13 in the Kapha type are significant, with X2 = 4.715 and p < 0.05. HLA DRB1*10 had higher allele frequency in the Kapha type than in the Pitta and Vata types. CONCLUSION: Ayurveda classifies the whole human population in three major constitutions as Vata, Pitta, Kapha and their possible combinations. Their homologous relation to human genetic structure needs to be studied for validation. If validated, our hypothesis would have far reaching implications for pharmacogenomics, modern genetics, human health, and Ayurveda.