Berberine as Adjuvant Treatment for Schizophrenia Patients (BER)

January 18, 2021 updated by: Prof. Zhang Zhang-Jin, The University of Hong Kong

A Double-blind, Randomized, Placebo-controlled Trial of Berberine as an Adjuvant to Treat Antipsychotic-induced Metabolic Syndrome in Patients With Schizophrenia Spectrum Disorders

One double-blind, randomized, placebo-controlled trial is designed to examine whether berberine added to current antipsychotic drugs could produce significantly greater efficacy in reducing atypical antipsychotic-induced metabolic syndrome. To achieve this objective, 120 patients with schizophrenia spectrum disorders (SSD) who have developed metabolic syndrome will be recruited and randomly assigned to receive additional treatment with placebo (n = 60) or berberine (n = 60, 0.6 g/day, 0.3 g, b.i.d.) for 12 weeks. The primary outcome is changes in net weight gain; other outcomes include body mass index (BMI), waist circumference (WC), blood pressure, triglycerides (TG), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), fasting glucose, glycated haemoglobin (HbA1c).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Schizophrenia is a severe mental illness that affects about 1% of the worldwide population. Most patients develop a chronic course with frequent relapses and exacerbation of symptoms and required to have long-term treatment. Although antipsychotic therapy is the mainstay of the management of schizophrenia, the treatment outcomes are often unsatisfactory, largely due to adverse drug reactions. Metabolic syndrome is a highly prevalent side effect incurred in antipsychotic therapy, with a prevalence of 35% in patients with severe mental illness in Hong Kong. No effective therapies are available in treating antipsychotic-induced metabolic syndrome, although some antidiabetic medications may have limited benefits in controlling weight gain and increased glucose level.

Berberine is a natural plant alkaloid isolated from the Chinese herb, Coptis chinensis (Huang-Lian), which is traditionally used for diarrhea caused by bacterial and viral infections in clinical practice. Several lines of evidence suggest that berberine has body weight-lowering, anti-diabetic, and anti-hyperlipidemic effects. One recent study has further shown that the addition of berberine significantly prevented olanzapine (OLZ)-Induced weight gain in rats and modulated the expression of multiple key genes that control energy expenditure.

In addition to the peripheral effects, berberine also broadly modulates brain biogenic amines and related receptors that are involved in the pathogenesis of antipsychotic-induced metabolic syndrome. This suggests that it may be suitable for the treatment of antipsychotic-induced metabolic disturbance.

Over the past decade, a number of studies have demonstrated comparable efficacy of berberine as mono- and combination therapy in reducing metabolic symptoms, without serious side effect. The efficacy of berberine also has been well confirmed in patients with gastrointestinal, liver, heart, and ovary disease as well as in renal-transplant recipients and healthy volunteers. It is well tolerated and only minor digestive reactions were observed, mainly nausea, diarrhea, constipation, abdominal distension and pain.

The results obtained from the clinical and animal studies of the group strongly suggest the promising effects of berberine against OLZ-induced weight gain, without changing pharmacokinetic and pharmacodynamics profile of OLZ at peripheral and central levels. This warrants further evaluation in a larger randomized controlled trial.

The working hypothesis of the proposed study is that berberine as an adjuvant can control weight gain and other metabolic symptoms associated with antipsychotic therapy. To test this hypothesis, a 12-week, double-blind, randomized, placebo-controlled trial will be conducted in patients with schizophrenia spectrum disorders (SSD) to determine whether berberine adjunctive treatment could limit weight gain and improve other anthropometric and metabolic measures in patients with SSD who have developed metabolic syndrome.

Study Type

Interventional

Enrollment (Actual)

113

Phase

  • Phase 2
  • Phase 3

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

  • Hong Kong
      • Tuen Mun, Hong Kong
        • Castle Peak Hospital - The Department of General Adult Psychiatry

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • a primary diagnosis of SSD, including schizophrenia, schizoaffective disorder, schizophreniform disorder, and psychotic disorder not otherwise specified according to the Classification of Mental and Behavior Disorders (10th version);
  • have been under atypical antipsychotic treatment for at least 3 months and current conditions are stable, indicated by no difficulty to communicate with investigators and give informed consent; and
  • have developed metabolic syndrome according to the International Diabetes Federation criteria for metabolic syndrome in Asian/Chinese population.

Exclusion Criteria:

  • serious comorbid gastrointestinal or other unstable medical conditions;
  • have suicidal ideas or attempts or aggressive behavior;
  • have a history of alcohol abuse in the past 3 months;
  • have a history of drug abuse in past 3 months;
  • had an investigational drug treatment within the previous 6 months; or
  • pregnant and lactation.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Berberine
Patients will receive berberine pills in additional to current atypical antipsychotic agents
Drug: Berberine
Berberine tablets, 0.3g every time, two times daily
Drug: Antipsychotic Agents
Antipsychotic agents prescribed at the discretion of the patients' psychiatrists with respect to patients' conditions. Concomitant use of other psychotropic drugs, including antidepressants, anxiolytics, and mood stabilizers for mood disorders, benzodiazepines and non-benzodiazepines for insomnia, and anticholinergics for extrapyramidal symptoms, was allowed as usual. For those who were under anti-hyperlipidemic, antihypertensive and anti-diabetic treatment, they were allowed to continue their current medications throughout the study.
Placebo Comparator: Placebo
Patients will receive placebos pills in additional to current atypical antipsychotic agents
Drug: Antipsychotic Agents
Antipsychotic agents prescribed at the discretion of the patients' psychiatrists with respect to patients' conditions. Concomitant use of other psychotropic drugs, including antidepressants, anxiolytics, and mood stabilizers for mood disorders, benzodiazepines and non-benzodiazepines for insomnia, and anticholinergics for extrapyramidal symptoms, was allowed as usual. For those who were under anti-hyperlipidemic, antihypertensive and anti-diabetic treatment, they were allowed to continue their current medications throughout the study.
Drug: Placebos
Placebo tablets, 0.3g every time, two times daily
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in net weight gain
Time Frame: Baseline, 3 week, 6 week, 9 week, 12 week
Assessments will be conducted at baseline and once every three weeks thereafter.
Baseline, 3 week, 6 week, 9 week, 12 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in body mass index (BMI)
Time Frame: Baseline, 3 week, 6 week, 9 week, 12 week
Assessments will be conducted at baseline and once every three weeks thereafter.
Baseline, 3 week, 6 week, 9 week, 12 week
Changes in waist circumference (WC)
Time Frame: Baseline, 3 week, 6 week, 9 week, 12 week
Assessments will be conducted at baseline and once every three weeks thereafter.
Baseline, 3 week, 6 week, 9 week, 12 week
Changes in blood pressure
Time Frame: Baseline, 6 week, 12 week
Assessments will be conducted at baseline and once every six weeks thereafter.
Baseline, 6 week, 12 week
Changes in triglycerides (TG)
Time Frame: Baseline, 12 week
Triglycerides (TG) level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in total cholesterol
Time Frame: Baseline, 12 week
Total cholesterol level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in high-density lipoprotein (HDL)
Time Frame: Baseline, 12 week
High-density lipoprotein (HDL) level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in low-density lipoprotein (LDL)
Time Frame: Baseline, 12 week
Low-density lipoprotein (LDL) level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in fasting glucose
Time Frame: Baseline, 12 week
Fasting glucose level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in glycated haemoglobin (HbA1c)
Time Frame: Baseline, 12 week
Glycated haemoglobin (HbA1c) level will be determined from blood samples collected at baseline and 12 weeks. The collection of blood will be conducted between 08:00 and 09:00 after an overnight fast.
Baseline, 12 week
Changes in positive and Negative Syndrome Scale (PANSS)
Time Frame: Baseline, 6 week, 12 week
The severity of psychotic symptoms will be also assessed using the Positive and Negative Syndrome Scale (PANSS). Assessments will be conducted at baseline and once every six weeks thereafter.
Baseline, 6 week, 12 week
Changes in extrapyramidal Symptom Rating Scale (ESRS)
Time Frame: Baseline, 6 week, 12 week
The Extrapyramidal Symptom Rating Scale (ESRS) will be used to evaluate antipsychotic-induced movement symptoms. Assessments will be conducted at baseline and once every six weeks thereafter.
Baseline, 6 week, 12 week

Collaborators and Investigators

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

Sponsor

The University of Hong Kong

Collaborators

Queen Mary Hospital, Hong Kong
Kowloon Hospital, Hong Kong
Castle Peak Hospital
Zhejiang Provincial Tongde Hospital

Investigators

  • Principal Investigator: Zhang-Jin Zhang, MMed, PhD, School of Chinese Medicine, The University of Hong Kong

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)

April 25, 2018

Primary Completion (Actual)

December 30, 2020

Study Completion (Actual)

January 4, 2021

Study Registration Dates

First Submitted

November 29, 2016

First Submitted That Met QC Criteria

December 5, 2016

First Posted (Estimate)

December 6, 2016

Study Record Updates

Last Update Posted (Actual)

January 22, 2021

Last Update Submitted That Met QC Criteria

January 18, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 17-020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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