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History of Changes for Study: NCT04950803
A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Recovered COVID-19 Patients
Latest version (submitted July 19, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 2, 2021 None (earliest Version on record)
2 February 13, 2022 Contacts/Locations and Study Status
3 February 7, 2023 Outcome Measures and Study Status
4 July 19, 2023 Recruitment Status, Study Status, Contacts/Locations, Arms and Interventions, Outcome Measures, Study Design and Study Description
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Changes (Merged) for Study: NCT04950803
July 2, 2021 (v1) -- July 19, 2023 (v4)

Changes in: Study Status, Study Description, Study Design, Arms and Interventions, Outcome Measures and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: RECOVERY
Brief Title: A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Recovered COVID-19 Patients
Official Title: A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Reducing Development of Long-term Co-morbidities in Recovered COVID-19 Patients
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2021 2023
Overall Status: Recruiting Active, not recruiting
Study Start: June 25, 2021
Primary Completion: May 31, 2025 [Anticipated]
Study Completion: December 31, 2025 [Anticipated]
First Submitted: June 21, 2021
First Submitted that
Met QC Criteria:
July 2, 2021
First Posted: July 6, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
July 2 19, 2021 2023
Last Update Posted: July 6 21, 2021 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Chinese University of Hong Kong
Responsible Party: Principal Investigator
Investigator: Siew Chien NG
Official Title: Professor
Affiliation: Chinese University of Hong Kong
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: This study aims to evaluate the effectiveness of an oral microbiome immunity formula in modulating gut microbiota, enhancing immunity and reducing long-term complications and co-morbidities in patients who have recovered from COVID-19.
Detailed Description:

SARS-CoV-2, the cause of COVID-19, emerged as a new zoonotic pathogen of humans at the end of 2019 and rapidly developed into a global pandemic. It may develop severe or critical disease with respiratory failure requiring oxygen support and intensive care.

Natural infection by virus triggers an effective system immunity so that the host can resist or highly reduce the chance of re-infection.

In many cases, this protection can maintain a long period of time. However, the long-term immunities (over a year) and complications from the patients are not yet very clear. We found that COVID-19 survivors who have cleared the virus continued to have persistent altered gut microbiota and up to 80 percent had residue COVID-19 related symptoms including fatigue, difficulty in breathing, impaired memory and hair loss up to 6 months after discharge (LONG COVID-19).

Earlier studies from our CU Medicine have shown a link between altered gut microbiome and COVID-19 severity, and more patients who received a novel microbiome immunity formula (SIM01) achieved complete symptom resolution and developed neutralising antibody than those who did not (unpublished data). Research from the Faculty also reported that almost 40% of people in Hong Kong had significant gut dysbiosis especially in elderly and patients with diabetes, obesity or chronic diseases.

This study is a multi- single-centre, triple-blind, randomized, placebo-controlled clinical trial that aims to evaluate the effectiveness of an oral microbiome immunity formula (SIM01) invented by the Chinese University of Hong Kong (CUHK) in modulating gut microbiota, enhancing immunity and reducing long-term complications and co-morbidities (e.g. sepsis, cardiopulmonary complications, metabolic syndrome, neuropsychiatric disorders) in patients who have recovered from COVID-19.

Open or close this module Conditions
Conditions: COVID-19
Probiotic
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Prevention
Study Phase: Not Applicable
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Triple (Participant, Care Provider, Investigator)
Allocation: Randomized
Enrollment: 280 448 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Active arm
Subjects will take microbiome immunity formula (SIM01) daily for 3 6 months
Dietary Supplement: Microbiome immunity formula
Microbiome immunity formula contains probiotics blend (3Bifidobacteria, 10 20 billion CFU per sachet daily)
Placebo Comparator: Placebo arm
Subjects will take active vitamin daily for 3 6 months
Dietary Supplement: Active placebo
Active placebo contains active vitamin
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Any comorbidities Alleviation of symptoms or complications
[ Time Frame: 6 months ]

A composite outcome of any comorbidities, including clinical manifestations of long-COVID, hospitalizations due to sepsis, cardiopulmonary complications, metabolic syndrome and neuropsychiatric disorders Proportion of subjects with alleviation of symptoms or complication of post-COVID conditions within 6 months.
Secondary Outcome Measures:
1. Any comorbidities
[ Time Frame: 24 months ]

A composite outcome of any comorbidities, including clinical manifestations of long-COVID, hospitalizations due to sepsis, cardiopulmonary complications, metabolic syndrome and neuropsychiatric disorders
2. Increase in metabolic syndrome (MetS) score
[ Time Frame: 24 months ]

a validated index computed from an analysis based on waist circumference, fasting triglycerides, fasting glucose, and systolic blood pressure, calculated in score (1-5), higher levels indicated higher probability of presence of metabolic syndrome
3. Increase in other system-specific comorbidities
[ Time Frame: 24 months ]

Increase in other system-specific comorbidities involving cardiovascular, gastrointestinal, liver, renal, genitourinary, haematological, and neurological systems
4. Healthcare service utilization
[ Time Frame: 24 months ]

The frequency of healthcare service (including clinics and Accident and Emergency) that the subject has attended
5. Self-reported long-COVID-19 symptoms
[ Time Frame: 24 months ]

Subjects will fill in a survey whether they have long-COVID-19 symptoms (e.g. cough, fatigue, etc) and grade the symptoms. The higher the score, the worse the outcome.
6. Changes in Quality of life
[ Time Frame: 48 months ]

Changes in Quality of life using visual analogue scale, score ranging 0-100. The higher the score, the better the outcome.
7. Changes in faecal microbial and bacterial metabolites
[ Time Frame: 48 months ]

Shotgun metagenomics and metabolomics sequencing of faecal samples at baseline and each visit will be used to generate serial gut microbial taxonomic and bacterial functional profiles.
8. Blood immunity profiles
[ Time Frame: 24 months ]

To characterize immune cell phenotypes in peripheral blood mononuclear cells (PBMCs), we will evaluate multiple cytokines and chemokines in plasma samples using MILLIPLEX MAP Human Cytokine/ Chemokine Magnetic Bead Panel. Inflammatory cytokines in plasma samples will be identified and quantified using human inflammation panel 1 (13-plex) of LEGENDplex
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Individuals aged 18 and above;
  2. Subjects who are mentally capable to participate in the study and provide informed consent;
  3. Subjects who can communicate in Chinese or English;
  4. Subjects who are ambulatory and do not have difficulties travelling to the clinics for follow-up;
  5. Subjects who do not have plans to leave Hong Kong in the subsequent two years after recruitment; and
  6. Subjects who agree to give informed consent voluntarily.

Exclusion Criteria:

  1. Subjects who are unable to receive oral fluids;
  2. Subjects who have received surgery involving the intestine within past 30 days;
  3. Subjects who are pregnant or breastfeeding; and
  4. Subjects who are immunocompromised, e.g. on cancer treatment, bone marrow/organ transplant, immune deficiency, poorly controlled HIV/AIDS.
Open or close this module Contacts/Locations
Central Contact Person: Kristy Ho
Telephone: 35053855
Email: hiutungho@cuhk.edu.hk
Central Contact Backup: Amy Li
Telephone: 26373225
Email: amyli@cuhk.edu.hk
Study Officials: Siew Ng
Principal Investigator
CUHK-M&T
Locations: Hong Kong
Prince of Wales Hospital
[Recruiting]
Hong Kong, Hong Kong
Contact:Contact: Siew Chien Ng, PhD 35053996 siewchienng@cuhk.edu.hk
Prince of Wales Hospital
Hong Kong, Hong Kong
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
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Links: Description: WHO website
Description: Hong Kong Government website
Description: Quality of Life and Long-term Outcomes After Hospitalization for COVID-19.
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