The Effect of Berberine on Intestinal Function and Inflammatory Mediators in Severe Patients With Covid-19 (BOIFIM)

July 19, 2020 updated by: Chinese Medical Association
Coronavirus disease 2019 (COVID-19) rapidly spread across China and throughout the world, causing hundreds of thousands died. Studies had shown that "cytokine storms" and subsequent multiple organ dysfunction (MODS) are important causes for disease progression and death in patients with COVID-19. Similar to SARS-CoV infection, SARS-CoV-2 would infect humans via binding of S-protein to angiotensin-converting enzyme 2 (ACE2), a host cell receptor, and the S protein is activated and cleaved by cellular transmembrane serine proteases, allowing the virus to release fusion peptides for membrane fusion. In addition to the lungs, ACE2 is also highly expressed in the esophagus, small intestine and colon, suggesting that the gut might also be an important target organ for SARS-CoV-2. About 8-16% of severe pneumonia cases confirmed with SARS-CoV-2 infection developed gastrointestinal symptoms such as abdominal pain, vomiting, and diarrhea. Moreover, the stool of patient with COVID-19 also positive by real-time reverse-transcriptase-polymerase-chain-reaction (rRT-PCR) assay. Furthermore, elevated faecal calprotectin was observed in patients with COVID-19 suggested an inflammatory response in the gut, which was significantly correlated with IL-6. For severe and critical cases, control "cytokine storms" and maintain intestinal microenvironment balance have been included into the Diagnosis and Treatment Guideline of patients with COVID-19 (Edition 7). Berberine is a quaternary ammonium alkaloid isolated from rhizoma coptidis. It is often used in treatment of infectious diarrhea by bacteriostasis and inhibition of intestinal gland secretion. Berberine has also been found to have a role in intestinal immune regulation, inhibiting both AP-1 and NF- B, the key factors in cell signal transduction, and reducing the inflammatory response. Investigators conducted a prospective randomized controlled clinical trial to investigate the effects of berberine on intestinal function, serum concentrations of the inflammatory biomarkers, and organ function in severe patients with SARS-CoV-2 infection.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients aged 18-80 years who confirmed with COVID-19 and classified as severe were enrolled in the study, and then separated randomly into two groups: a berberine group (B group) and a control group (C group). The diagnostic criteria for severe cases are in accordance with the Diagnosis and Treatment Guideline of patients with COVID-19 issued by the National Health Commission of the People's Republic of China (Edition 7). In general, patients diagnosed with COVID-19 pneumonia must also meet any of the following criteria: appears shortness of breath, respiratory rate (RR) ≥ 30 times/min; SPO2 ≤ 93% at rest; the ratio of partial oxygen pressure of arterial blood (PaO2) to oxygen absorption concentration (FiO2) ≤ 300mmHg (1mmHg=0.133KPa); pulmonary imaging showed the lesion progression >50% within 24-48 hours. All enrolled patients were given general support therapy, oxygen therapy, antiviral drugs, in combination with antibiotics and small doses of glucocorticoids if necessary, nutritional and organ function support. Patients in the berberine group (B group) were given berberine 0.3g tid orally or tube feed daily, while patients in the control group (C group) were given montmorilonite orally if they presence of diarrhea. The duration of the study intervention was 14 days and followed up to discharge. Investigators record general information about patients at admission, including age, gender, age, exposure history, time from onset of symptoms to hospital, APACHE II score, the presentation of X-ray, comorbidity, mechanical ventilation, fever or not,gastrointestinal symptoms. Investigators also evaluate the gastrointestinal function daily,including gastrointestinal symptoms (nausea, vomiting, abdominal pain, abdominal distension or diarrhoea), frequency of diarrhea, the characteristics of stool (Bristol scal). Peripheral blood are collected on day 1,3, 7 and 14 after admission to determine the level of interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α). Laboratory tests are also performed to evaluate leucocyte, c-reactive protein (CRP), and procalcitonin (PCT) levels at the same time. Glutamate transaminase (ALT), glutamate transaminase (AST), urea nitrogen (Bun), creatinine, prothrombin time (PT), partially activated prothrombin time (APTT), and Sequential Organ Failure Assessment (SOFA) score are used to evaluate organ function on day 1,3, 7 and 14 after admission. Investigators also record the adverse events associated with the drug, length of stay and the prognosis at discharge. The patients are blinded to the group allocation. Two physicians are responsible for data processing, one is responsible for recording and collecting, and the other is responsible for checking, and they are all blind to the research.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210008
        • Nanjing Drum Tower Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients confirmed with COVID-19 and classified as severe

Exclusion Criteria:

  • inflammatory bowel disease;
  • have other sources of infection;
  • death is anticipate within 72 hours;
  • participated in other clinical trials;
  • pregnant or lactating women;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: berberine group (B group)
Patients in the B group were given berberine hydrochloride tables 0.3g tid orally or tube feed daily, until the 14th day of the study. Other treatments include general support therapy, oxygen therapy, antiviral drugs, in combination with antibiotics and small doses of glucocorticoids if necessary, nutritional and organ function support.
Drug: Berberine
Patients in the intervention group received berberine daily, regardless of gastrointestinal symptoms.If the patient has a serious drug-related adverse event, the drug will be discontinued and the patient will be excluded from the study.
Other Names:
  • Berberine Hydrochloride Tablets
Sham Comparator: control group (C group)
Patients in the C group were given montmorilonite orally if they presence of diarrhea. The other treatments were the same as in B group.
Drug: Montmorrillonite
Patients in the control group were routinely not given special treatment.However, if the patient has diarrhea symptoms, montmorillonite powder should be given orally.
Other Names:
  • Montmorrillonite Powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in diarrhea frequency and Bristol Stool Scale
Time Frame: daily, from date of randomization until the date of discharge or date of death from any cause, assessed up to 2 weeks.
Including diarrhea in times/day, Bristol Stool Scale (the minimum 1 and maximum 7, a higher scores mean a worse outcome) and whether patient has any one of gastrointestinal symptoms (nausea, vomiting, abdominal pain, abdominal distension or diarrhoea).
daily, from date of randomization until the date of discharge or date of death from any cause, assessed up to 2 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
IL-6 (ng/ml)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
IL-10（ng/ml）
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
IL-1β (ng/ml)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
TNF-α (pg/ml)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
leukocyte count (10^9/l)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
c reactive protein (mg/l)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
procalcitonin (ng/ml)
Time Frame: baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause
evaluate inflammatory response, blood sample collected at 6:00am
baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sequential Organ Failure Assessment (SOFA) score
Time Frame: baseline (at admission), day 3, 7 and 14 after admission or until the date of discharge or date of death from any cause
evaluate the severity of the disease(the minimum 0 and maximum 24, a higher scores mean a worse outcome)
baseline (at admission), day 3, 7 and 14 after admission or until the date of discharge or date of death from any cause

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese Medical Association

Investigators

  • Study Chair: Wenkui Yu, M.D., The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 8, 2020

Primary Completion (Actual)

April 18, 2020

Study Completion (Actual)

April 23, 2020

Study Registration Dates

First Submitted

May 13, 2020

First Submitted That Met QC Criteria

July 19, 2020

First Posted (Actual)

July 21, 2020

Study Record Updates

Last Update Posted (Actual)

July 21, 2020

Last Update Submitted That Met QC Criteria

July 19, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Berberine treats COVID-19
  • XJ2020005101 (Other Grant/Funding Number: The fundamental Resrarch Funds for the Central Universities)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

We have other articles about covid-19 yet to be published

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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