Evaluation of a Synbiotic Formula in Patient With COVID-19

Coronavirus Clinical Trial

Official title:

Evaluation of a Synbiotic Formula in Patient With COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04730284
• Other study ID #: COVSyn
• Status: Recruiting
• Phase: N/A
• Start date: August 25, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: January 2021
• Source: Chinese University of Hong Kong
• Contact: Kristy Ho, Bsc
• Phone: 85235053855
• Email: hiutungho[@]cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Coronavirus can target multiple organs due to the hyperactive immune response with cytokine storms. Several studies have detected SARS-CoV-2 in stool samples and indicated that the virus could spread via faeces. Importantly, COVID-19 uses the same receptor as SARS and this doorway can also be found in the intestine. The cell entry receptor, known as angiotensin converting enzyme 2 (ACE2) receptor mediate entry of SARS-CoV-2 and is highly expressed in small bowel enterocytes. ACE2 is important in controlling intestinal inflammation and its disruption may lead to diarrhoea. 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 billion confirmed cases globally with 620 thousand deaths. Currently, there are more than 2000 confirmed cases of COVID-19 in Hong Kong. It is important to rebalance the gut microbiota in COVID-19 patients and to improve the symptoms and the quality of life of these patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 31, 2022
• Est. primary completion date: September 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 and released from isolation at recruitment.

3. Written informed consent obtained

Exclusion Criteria:

1. Known allergy or intolerance to the intervention product or its components

2. 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)

3. 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

4. Known increased infection risk due to endovascular due to:

• Rheumatic heart disease
• Congenital heart defect,
• Mechanical heart valves
• Endocarditis
• Endovascular grafts
• Permanent endovascular devices such as permanent (not short-term) hemodialysis catheters, pacemakers, or defibrillators

5. Documented pregnancy

Related Conditions & MeSH terms

• Coronavirus
• Coronavirus Infections

Intervention

Other:
• Health supplements
tailor-made Synbiotics, 4g per day for 28 days

Locations

Country	Name	City	State
Hong Kong	Chinese University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (12)

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18. — View Citation

Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G, Merson L, Lee J, Plotkin D, Sigfrid L, Halpin S, Jackson C, Gamble C, Horby PW, Nguyen-Van-Tam JS, Ho A, Russell CD, Dunning J, Openshaw PJ, Baillie JK, Semple MG; ISARIC4C investigators. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020 May 22;369:m1985. doi: 10.1136/bmj.m1985. — View Citation

Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V, Hanada T, Hanada R, Lipinski S, Wild B, Camargo SM, Singer D, Richter A, Kuba K, Fukamizu A, Schreiber S, Clevers H, Verrey F, Rosenstiel P, Penninger JM. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012 Jul 25;487(7408):477-81. doi: 10.1038/nature11228. — View Citation

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, Diaz G, Cohn A, Fox L, Patel A, Gerber SI, Kim L, Tong S, Lu X, Lindstrom S, Pallansch MA, Weldon WC, Biggs HM, Uyeki TM, Pillai SK; Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020 Mar 5;382(10):929-936. doi: 10.1056/NEJMoa2001191. Epub 2020 Jan 31. — View Citation

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 30;:. — View Citation

Janowitz T, Gablenz E, Pattinson D, Wang TC, Conigliaro J, Tracey K, Tuveson D. Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series. Gut. 2020 Sep;69(9):1592-1597. doi: 10.1136/gutjnl-2020-321852. Epub 2020 Jun 4. — View Citation

Liang W, Feng Z, Rao S, Xiao C, Xue X, Lin Z, Zhang Q, Qi W. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020 Jun;69(6):1141-1143. doi: 10.1136/gutjnl-2020-320832. Epub 2020 Feb 26. — View Citation

WHO Coronavirus Disease (COVID-19) Dashboard. [Assessed on 24 Jul 2020]. https://covid19.who.int/

Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, Lit LC, Hui DS, Chan MH, Chung SS, Sung JJ. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004 Apr;136(1):95-103. — View Citation

Yeo C, Kaushal S, Yeo D. Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible? Lancet Gastroenterol Hepatol. 2020 Apr;5(4):335-337. doi: 10.1016/S2468-1253(20)30048-0. Epub 2020 Feb 20. — View Citation

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24. — View Citation

Zuo T, Zhan H, Zhang F, Liu Q, Tso EYK, Lui GCY, Chen N, Li A, Lu W, Chan FKL, Chan PKS, Ng SC. Alterations in Fecal Fungal Microbiome of Patients With COVID-19 During Time of Hospitalization until Discharge. Gastroenterology. 2020 Oct;159(4):1302-1310.e5. doi: 10.1053/j.gastro.2020.06.048. Epub 2020 Jun 26. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in gut microbiome	Changes in the gut microbiome (bacteria, virome and fungome) measured by metagenomics at week 5 compared to baseline	week 5
Secondary	Changes in fecal bacteria metabolites	Changes in fecal bacteria metabolites by PCR at different time points	weeks 2, 4, 5, 8 and months 3, 6, 9 and 12
Secondary	Change in plasma cytokines including IL-6, IL-IB, TNF-a and CXCL-10	Change in plasma cytokines level at week 5 compared with baseline	week 5
Secondary	Trend in symptom score	Trend of symptom score at different time points, ranges from 26-104. The higher the score, the worse the symptoms.	weeks 2, 4, 5, 8 and months 3, 6, 9 and 12
Secondary	Change in Quality of life measured by EQ-5D-5L	Change in score on Quality of life using EQ-5D-5L at different time points. 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).	weeks 2, 4, 5, 8 and months 3, 6, 9 and 12
Secondary	Change in Quality of life measured by SF-12	Change in score on Quality of life using SF-12 at different time points. 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.	weeks 2, 4, 5, 8 and months 3, 6, 9 and 12
Secondary	Duration of gastrointestinal symptoms	Duration of gastrointestinal symptoms such as anorexia, nausea, vomiting, abdominal pain, bloating within 4 weeks.	4 weeks
Secondary	Adverse event assessment	Number of adverse event	3 months