History of Changes for Study: NCT04950803

A Randomised-controlled Trial of an Oral Microbiome Immunity Formula in Recovered COVID-19 Patients

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Study Record Versions

Version	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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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:

Study Status


Record Verification:	February 2022
Overall Status:	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:	February 13 7, 2022 2023
Last Update Posted:	February 15 9, 2022 2023 [Actual]

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:

Oversight


U.S. FDA-regulated Drug:	No
U.S. FDA-regulated Device:	No
Data Monitoring:

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-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.

Conditions


Conditions:	COVID-19 Probiotic
Keywords:

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 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Active Comparator: Active arm Subjects will take microbiome immunity formula (SIM01) daily for 3 months	Dietary Supplement: Microbiome immunity formula Microbiome immunity formula contains probiotics blend (3Bifidobacteria, 10 billion CFU per sachet)
Placebo Comparator: Placebo arm Subjects will take active vitamin daily for 3 months	Dietary Supplement: Active placebo Active placebo contains active vitamin

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.

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Individuals aged 18 and above; Subjects who are mentally capable to participate in the study and provide informed consent; Subjects who can communicate in Chinese or English; Subjects who are ambulatory and do not have difficulties travelling to the clinics for follow-up; Subjects who do not have plans to leave Hong Kong in the subsequent two years after recruitment; and Subjects who agree to give informed consent voluntarily. Exclusion Criteria: Subjects who are unable to receive oral fluids; Subjects who have received surgery involving the intestine within past 30 days; Subjects who are pregnant or breastfeeding; and Subjects who are immunocompromised, e.g. on cancer treatment, bone marrow/organ transplant, immune deficiency, poorly controlled HIV/AIDS.

Contacts/Locations


Central Contact Person:	Rain Leung Telephone: 26373225 Email: yutungleung@cuhk.edu.hk
Central Contact Backup:	Matthew Fung Telephone: 35053855 Email: mfung@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

IPDSharing


Plan to Share IPD:

References


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Links:	URL: https://www.who.int/emergencies/diseases/novel-coronavirus-2019 Description: WHO website
	URL: https://www.coronavirus.gov.hk/eng/index.html Description: Hong Kong Government website
	URL: https://clinicaltrials.gov/ct2/show/NCT04376658?cond=long+covid+outcome&draw=2&rank=2 Description: Quality of Life and Long-term Outcomes After Hospitalization for COVID-19.
Available IPD/Information: