Clinical trial NCT04884776: Modulation of Gut Microbiota to Enhance Health and Immunity
Official title: Modulation of Gut Microbiota to Enhance Health and Immunity of Vulnerable Individuals During COVID-19 Pandemic
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gut Microbiota
COVID-19 Vaccine
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2021-05-13
Enrollment: 453
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

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, chemotherapies 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. Known active malignancy
7. Known terminal illness with life expectancy less than 3 months

Primary outcomes:
measure: Adverse events/Serious adverse events
timeFrame: within 6 months
Secondary outcomes:
measure: Immunogenicity of the COVID-19 vaccine
timeFrame: 3 months and 6 months
measure: Change in gut microbiome
timeFrame: 1, 3, 6, and 12 months
measure: Changes in plasma inflammatory cytokines
timeFrame: 3 months and 6 months
measure: Restoration of gut dysbiosis
timeFrame: 1, 3, 6 and 12 months
measure: Number of unscheduled hospitalisation and clinic visits
timeFrame: 1, 3, 6, and 12 months
measure: Changes of quality of life
timeFrame: 1, 3, 6, and 12 months
measure: Changes in glycaemic control
timeFrame: 1, 6 and 12 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital, Shatin
Study officials:
affiliation: Chinese University of Hong Kong
name: Joyce WY Mak, FHKAM
role: PRINCIPAL_INVESTIGATOR
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