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

NCT04479202 | Completed Phase 4

• 2 other identifiers: Berberine treats COVID-19XJ2020005101
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Berberine; COVID-19

Keywords

Gastrointestinal function; inflammatory biomarkers; Organ function

Outcome Measures

Primary Outcomes (1)

• Changes in diarrhea frequency and Bristol Stool Scale

  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 Outcomes (7)

• IL-6 (ng/ml)

  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）

  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)

  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)

  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)

  baseline (at admission), day 3,7 and14 after admission or until the date of discharge or date of death from any cause

Other Outcomes (1)

• Sequential Organ Failure Assessment (SOFA) score

  baseline (at admission), day 3, 7 and 14 after admission or until the date of discharge or date of death from any cause

Study Arms (2)

berberine group (B group)

EXPERIMENTAL

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

control group (C group)

SHAM COMPARATOR

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

Interventions

Berberine DRUG

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.

Also known as: Berberine Hydrochloride Tablets

berberine group (B group)

Montmorrillonite DRUG

Patients in the control group were routinely not given special treatment.However, if the patient has diarrhea symptoms, montmorillonite powder should be given orally.

Also known as: Montmorrillonite Powder

control group (C group)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients confirmed with COVID-19 and classified as severe

You may not qualify if:

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

Sponsors & Collaborators

• Chinese Medical Association: lead

Study Sites (1)

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

Location

Related Publications (3)

• Effenberger M, Grabherr F, Mayr L, Schwaerzler J, Nairz M, Seifert M, Hilbe R, Seiwald S, Scholl-Buergi S, Fritsche G, Bellmann-Weiler R, Weiss G, Muller T, Adolph TE, Tilg H. Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut. 2020 Aug;69(8):1543-1544. doi: 10.1136/gutjnl-2020-321388. Epub 2020 Apr 20. No abstract available.

  PMID: 32312790 RESULT

• Jin X, Lian JS, Hu JH, Gao J, Zheng L, Zhang YM, Hao SR, Jia HY, Cai H, Zhang XL, Yu GD, Xu KJ, Wang XY, Gu JQ, Zhang SY, Ye CY, Jin CL, Lu YF, Yu X, Yu XP, Huang JR, Xu KL, Ni Q, Yu CB, Zhu B, Li YT, Liu J, Zhao H, Zhang X, Yu L, Guo YZ, Su JW, Tao JJ, Lang GJ, Wu XX, Wu WR, Qv TT, Xiang DR, Yi P, Shi D, Chen Y, Ren Y, Qiu YQ, Li LJ, Sheng J, Yang Y. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut. 2020 Jun;69(6):1002-1009. doi: 10.1136/gutjnl-2020-320926. Epub 2020 Mar 24.

  PMID: 32213556 RESULT

• Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.

  PMID: 32171076 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

Berberine; Bentonite

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Aluminum Silicates; Aluminum Oxide; Aluminum Compounds; Inorganic Chemicals; Silicates; Minerals; Oxides; Oxygen Compounds; Silicic Acid; Silicon Dioxide; Silicon Compounds

Study Officials

• Wenkui Yu, M.D.

  The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: July 21, 2020
• Study Start: February 8, 2020
• Primary Completion: April 18, 2020
• Study Completion: April 23, 2020
• Last Updated: July 21, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)