Clinical trial NCT04420676: Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection
Official title: Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We hypothesize that the intake of Omni-Biotic® 10 AAD can reduce intestinal inflammation and improves dysbiosis in Covid-19 disease. We further hypothesize that Omni-Biotic® 10 AAD can reduce the duration of diarrhea, stool frequency, improve stool consistency, improve other gastrointestinal symptoms of Covid-19, reduce disease duration and severity.

The investigators aim to perform a randomized, double blind, placebo-controlled study using telemedicine in patients with Covid-19 disease.

Detailed description: The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in Wuhan, Hubei province in December 2019, spread throughout China in early 2020 and developed as a pandemic thereafter. Although the virus mainly causes respiratory symptoms, GI (gastrointestinal) presentations have been reported in and outside of China. Patients may present with anorexia, nausea, vomiting, diarrhea and abdominal discomfort. Also, faecal-oral transmission of the virus is currently discussed. Preliminary, unpublished data from China suggest that patients with GI symptoms may suffer more frequently from severe courses of the disease. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) for cellular entry. ACE2 is expressed in the small intestinal epithelia as well as in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Diarrhea is associated with prolonged symptoms and viral carriage.

Clinical information on the characteristics of Covid-19 diarrhea is scarce. The duration of diarrhea is around 4 days with 3-4 loose stools per day. Faecal calprotectin is elevated in stool of patients with Covid-19 diarrhea, indicating a relation between gastrointestinal symptoms and this well-established inflammation biomarker.

So far, no therapy is available for Covid-19 infection in general or for Covid-19 induced diarrhea. Rehydration and potassium monitoring should be performed as in all patients with diarrhea. It is important to underline that antivirals and antibiotics are often used for COVID-19 treatment or treatment of bacterial superinfections, involving a likely alteration of the gut microbiota and causing diarrhea. It is therefore plausible that the gut microbiota could be a new therapeutic target and that probiotics or synbiotics (combination of probiotics with prebiotics) could have a role in the management of these patients. The China's National Health Commission recommended the use of probiotics for the treatment of patients with severe COVID-19 in order to preserve intestinal balance and to prevent secondary bacterial infections without any available clinical studies to support this and probiotics apparently were used in Zhejiang during the Covid-19 pandemic. Although there is no specific data on the effects of probiotics on SARS-CoV2 infections, meta-analyses show that probiotics are effective in the treatment of upper respiratory tract infections and viral gastroenteritis of other origins. Furthermore, Enterococcus faecium has been shown to have antiviral effects in enteropathogenic coronavirus transmissible gastroenteritis virus infections in piglets. We therefore aim to assess the role of synbiotics in the therapy of Covid-19 infection with gastrointestinal symptoms.

Eligibility criteria: Inclusion criteria

* 18 years or older
* Covid-19 infection diagnosed by a positive SARS-Cov-2 PCR (Polymerase chain reaction) result from a nasopharyngeal swab
* Informed (tele)consent Exclusion criteria
* Pre-existing diarrhoea (including but not restricted to chronic inflammatory bowel disease, chronic diarrhea of other causes, acute diarrheal illness -4 to -1 week before inclusion)
* Antibiotic therapy -4 to -1 week before inclusion
* Probiotic treatment -4 to -1 week before inclusion
* Technical difficulties to perform telemedicine study visits

Primary outcomes:
measure: Stool calprotectin
timeFrame: 30 days
Secondary outcomes:
measure: Stool frequency
timeFrame: 30 days
measure: Stool consistency
timeFrame: 30 days
measure: Gastrointestinal symptoms
timeFrame: 30 days
measure: Duration of Covid-19 disease
timeFrame: 30 days
measure: Severity of Covid-19 disease
timeFrame: 30 days
measure: Diarrhea
timeFrame: 30 days
measure: Stool Zonulin
timeFrame: 30 days
measure: Microbiome composition
timeFrame: 30 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Internal Medicine, Medical University of Graz
Study officials:
References: