Gut Microbiota, COVID-19 Vaccine
Conditions
Brief summary
The novel coronavirus infection (COVID-19) caused by the SARS-CoV-2 virus is now a pandemic and has culminated major morbidity and mortality globally. Studies have shown that patients with underlying type 2 diabetes mellitus (DM), obesity, old age and hypertension had a higher risk of developing severe COVID-19 infection and mortality related to COVID-19.Emerging evidence has shown that gut microbiota plays an important role in the pathogenesis of COVID-19.
Detailed description
HYPOTHESIS We hypothesize that modulating the gut microbiota with a microbiome immunity formula can rebalance the gut microbiota in populations at risk of infection, like, patients with type 2 DM and elderlies and can lower the number of hospitalisation and reduce side effects associated with COVID-19 vaccination. AIM We aim to evaluate the efficacy of modulating gut microbiota with a microbiome immunity formula in vulnerable subjects (patients with underlying type 2 DM and elderlies) in improving immune functions, reducing adverse events associated with COVID-19 vaccinations and reducing hospitalisation in susceptible individuals during the COVID-19 pandemic. STUDY DESIGN This is a double-blinded, randomized, active-placebo controlled study comparing a microbiome immunity formula and placebo in enhancing immunity and reducing hospitalisation within one year. Except two kinds of subjects (Substudy 1: Patients with Type 2 DM and Substudy 2: Elderly individual) will be included in respective substudy, all other methodologies are the same. In each substudy, at least half of the recruited subjects will plan to receive COVID-19 vaccination and start to take the study products after vaccination. Recruited subjects will be randomised to receive a microbiome immunity formula or active placebo for 3 months, with another 9 months follow-up after completion of study products.
Interventions
DIETARY_SUPPLEMENTMicrobiome immunity formula
Microbiome immunity formula contains probiotics blend (3 Bifidobacteria, 10 billion CFU per sachet)
DIETARY_SUPPLEMENTActive placebo
Active placebo contains active vitamin
Sponsors
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Substudy 1 Inclusion Criteria: 1. Age 18 years - below 65 years 2. A confirmed diagnosis of type 2 DM for ≥ 3 months with stable control (i.e. no change in DM medications in recent 2 months) 3. Written informed consents obtained
Exclusion criteria
1. Known history of confirmed COVID-19 infection 2. Known active sepsis or active malignancy 3. Known increased infection risk due to underlying immunosuppressed state which includes: * Prior organ or hematopoietic stem cell transplant * Neutropenia with absolute neutrophil count (ANC) \<500 cells/ul at the time of study inclusion * Known HIV infection with CD4 \<200 cells/ul at the time of study inclusion * On concomitant immunosuppressants or corticosteroid at a dose of prednisolone equivalent dose 10mg or more for more than 3 months 4. Known history or active infective endocarditis 5. On peritoneal dialysis or haemodialysis 6. Documented pregnancy Substudy 2 Inclusion Criteria: 1. Age 65 years and above 2. Written informed consents obtained
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events/Serious adverse events | within 6 months | Proportion of patients who presented with new symptoms/diseases which exerted unfavourable impacts on subjects. Serious adverse events are those adverse clinical events that resulted in hospital admission and/or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in gut microbiome | 1, 3, 6, and 12 months | Measured the gut microbiome changes by metagenomic sequencing and metabolite profiling by targeted and/or untargeted metabolites profiling |
| Changes in plasma inflammatory cytokines | 3 months and 6 months | Measured the inflammatory cytokines (CRP or ESR) in blood result |
| Restoration of gut dysbiosis | 1, 3, 6 and 12 months | It is defined as improvement in (i) gut microbiome composition and diversity; (ii) functional potential (i.e., MetaCyc pathway abundances); and (iii) proliferation of beneficial bacteria genus (i.e., bifidobacteria, eubacterium, roseburia and other short-chain fatty acids producers |
| Immunogenicity of the COVID-19 vaccine | 3 months and 6 months | Measured by serum neutralization assay against pseudo virus and live virus, and IgM and IgG against receptor-binding domain \[RBD\] and S1 |
| Changes of quality of life | 1, 3, 6, and 12 months | Measured the score of EQ-5D-5L which measure the health-related quality of life |
| Changes in glycaemic control | 1, 6 and 12 months | Measured by HbA1c |
| Number of unscheduled hospitalisation and clinic visits | 1, 3, 6, and 12 months | Number of unscheduled hospitalisation and clinic visits |
Countries
Hong Kong
Outcome results
None listed