An Evaluation of a Synbiotic Formula for Patients With COVID-19 Infection

• ClinicalTrials.gov Identifier: NCT04581018
• Recruitment Status: Enrolling by invitation
• First Posted: October 9, 2020
• Last Update Posted: February 15, 2022
• Sponsor: Siew Chien NG
• Information provided by (Responsible Party): Siew Chien NG, Chinese University of Hong Kong

Study Description

Brief Summary:

In December 2019, a cluster of pneumonia cases of unidentified cause emerged in Wuhan,was identified as the culprit of this disease currently being identified as "Coronavirus Disease 2019" (COVID-19) by World Health Organization.

Coronavirus was found to not only target the patient's lungs but also multiple organs. Around 2-33% of Coronavirus Disease-19 patients developed gastrointestinal symptoms. Studies have shown that Severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) was found in patient's feces, suggesting that the virus can spread through feces. In our previous study, stool samples from 15 patients with COVID-19 were analysed. Depleted symbionts and gut dysbiosis were noted even after patients were detected negative of SARS-CoV-2. A series of microbiota were correlated inversely with the disease severity and virus load. Gut microbiota could play a role in modulating host immune response and potentially influence disease severity and outcomes.

The investigators are uncertain about the impact of synbiotic on patients with COVID-19. However, a therapeutic strategy aiming at investigating the gut Imicrobiota of patients with COVID-9 who take synbiotic or not, leading to lesser progression to severe disease, less hospital stay and improved quality of life.

Condition or disease	Intervention/treatment	Phase
Covid19; Microbiota	Other: Health supplements	Not Applicable

Detailed Description:

In December 2019, a cluster of pneumonia cases of unidentified cause emerged in Wuhan, Hubei province, China. In early January, a novel betacoronavirus forming another clade within the subgenus sarbecovirus, now named SARS-CoV-2, was identified as the culprit of this disease currently being identified as "Coronavirus Disease 2019" (COVID-19) by WHO.

Coronavirus was found to not only target the patient's lungs, but also multiple organs. Around 2-33% of COVID-19 patients developed gastrointestinal symptoms. Studies have shown that SAR-CoV-2 was found in patient's feces, suggesting that the virus can spread through feces. In our previous study, stool samples from 15 patients with COVID-19 were analysed. Depleted symbionts and gut dysbiosis were noted even after patients were detected negative of SARS-CoV-2. A series of microbiota were correlated inversely with the disease severity and virus load. Gut microbiota could play a role in modulating host immune response and potentially influence disease severity and outcomes.

In July 2020, there are more than 15 million confirmed cases globally with 620 thousand deaths. Currently, there are more than 2000 confirmed cases of COVID-19 in Hong Kong. The investigators are uncertain about the impact of synbiotic on patients with COVID-19. However, a therapeutic strategy aiming at investigating the gut Imicrobiota of patients with COVID-9 who take synbiotic or not, leading to lesser progression to severe disease, less hospital stay and improved quality of life.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: An Evaluation of a Synbiotic Formula for Symptom Improvement in Hospitalised Patients With COVID-19 Infection
• Actual Study Start Date: August 13, 2020
• Estimated Primary Completion Date: July 31, 2022
• Estimated Study Completion Date: July 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Health supplements + standard care; 28 days of health supplements (Synbiotic) daily plus standard care	Other: Health supplements; 28 days of health supplements (synbiotic), 4g daily
No Intervention: Standard care; No intervention

Outcome Measures

Primary Outcome Measures :

1. Combined symptom score [ Time Frame: 4 weeks ]
   Combined symptom score improvement of the first 4 weeks. Symptoms score assessment ranges from 20-80. The higher the score, the worse the symptoms.

Secondary Outcome Measures :

1. Clinical improvement [ Time Frame: 4 weeks ]
   Compare the number and severity of symptoms existing by checking the list in symptoms assessment such as cough, shortness of breath, fever and gastrointestinal symptoms like anorexia, nausea, vomiting, abdominal pain, bloating before and during the study
2. Time to develop antibody against SARS-CoV-2 [ Time Frame: 16 days ]
   Compare the time to develop antibody against SARS-CoV-2 in both group
3. Quality of life measured by EQ-5D-5L [ Time Frame: 4 weeks ]
   Improvement of quality of life measured by EQ-5D-5L. EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.The index can be calculated by deducting the appropriate weights from 1, the value for full health (i.e. state 11111). Each category ranges from 1 to 5. The small the number, the better the health. The EQ-VAS is a vertical visual analogue scale that ranges 0-100 (higher score indicates better imaginable health).
4. Quality of life measured by SF-12 [ Time Frame: 4 weeks ]
   Improvement of quality of life measured by SF-12. SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. There are formulas for transformation of scale scores so that they will range from 0-100. High score in functioning items indicates better functioning while high score in pain items indicates freedom from pain.
5. Duration of hospital stay [ Time Frame: up to 3 months ]
   Measure the duration of hospital stay in both group
6. Time to negative PCR [ Time Frame: through study completion, an average of 1 year ]
   Compare the time to negative PCR in both group
7. Trend of symptom score [ Time Frame: 4 weeks ]
   Trend of symptom score, ranges from 26-104. The higher the score, the worse the symptoms.
8. Gastrointestinal symptoms [ Time Frame: 4 weeks ]
   Duration of gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain, bloating within 4 week.
9. Changes in fecal bacteria metabolites [ Time Frame: weeks 2, 4, 5 and 8 months 3, 6, 9 and 12 ]
   Changes in fecal bacteria metabolites measured by PCR at different time points
10. Change in plasma cytokines level [ Time Frame: week 2 and week 5 ]
    Change in plasma cytokines level at week 2 and week 5 compared with baseline
11. Changes in the gut microbiome [ Time Frame: weeks 1, 2, 3, 4, 5, 8 and months 3, 6, 9 and 12 ]
    Changes in the gut microbiome (bacteria, virome and fungome) measured by metagenomics at different time points (weeks 1, 2, 3, 4, 5 and months 3, 6, 9 and 12) compared to baseline
12. Number of admission to Intensive Care Unit [ Time Frame: 4 weeks ]
    Number of admission to Intensive Care Unit
13. Number of subjects with home discharge [ Time Frame: 4 weeks ]
    Number of subjects with home discharge
14. Number of mortality [ Time Frame: 4 weeks ]
    Number of mortality
15. Number of days absent from work [ Time Frame: 3 months ]
    Number of days absent from work since admission
16. Change of quality of life questionnaire [ Time Frame: week 8, months 3, 6, 9 and 12 ]
    Change in score on Quality of life using EQ-5D-5L and SF-12. EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.The index can be calculated by deducting the appropriate weights from 1, the value for full health (i.e. state 11111). Each category ranges from 1 to 5. The small the number, the better the health. The EQ-VAS is a vertical visual analogue scale that ranges 0-100 (higher score indicates better imaginable health). While the SF-12 is a self-reported outcome measure assessing the impact of health on an individual's everyday life. There are formulas for transformation of scale scores so that they will range from 0-100. High score in functioning items indicates better functioning while high score in pain items indicates freedom from pain.
17. Number of adverse event [ Time Frame: 3 months ]
    Number of adverse event

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Aged 18 or above; and
2. A confirmed diagnosis of SARS-CoV-2 infection using the PCR according to the standard of according to Centre for Health Protection, Department of Health, HK at recruitment and that require admission to the hospitalization area; and
3. Written informed consent is obtained

Exclusion Criteria:

1. Subjects admitted to Intensive Care Unit or on ventilator
2. Known allergy or intolerance to the intervention product or its components
3. Any known medical condition that would prevent taking oral probiotics or increase risks associated with probiotics including but not limited to inability to swallow/aspiration risk and no other methods of delivery (e.g no G/J tube)

4. Known increased infection risk due to immunosuppression such as:

   • Prior organ or hematopoietic stem cell transplant
   • Neutropenia (ANC <500 cells/ul)
   • HIV and CD4 <200 cells/ul
5. Known history or active endocarditis
6. Recent on CAPD or hemodialysis-
7. Documented pregnancy

Contacts and Locations

Locations

Hong Kong

The Chinese University of Hong Kong

Sha Tin, Hong Kong, 000000

Sponsors and Collaborators

Siew Chien NG

Investigators

• Principal Investigator: Siew Chien Ng; Chinese University of Hong Kong

More Information

Publications:

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• Responsible Party: Siew Chien NG, Professor, Chinese University of Hong Kong
• ClinicalTrials.gov Identifier: NCT04581018
• Other Study ID Numbers: Synbiotic COV study
• First Posted: October 9, 2020
• Last Update Posted: February 15, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases