Berberine as Adjuvant Treatment for Schizophrenia Patients

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

Sponsors

Lead Sponsor: The University of Hong Kong

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

Source The University of Hong Kong
Brief Summary

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, 1.2 g/day, 0.4 g, t.i.d.) for 12 weeks. The primary outcome is weight gain; other outcomes include body mass index (BMI), waist circumference, blood pressure, triglycerides (TG), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL), fasting glucose, insulin, and insulin resistant index.

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.

Overall Status Recruiting
Start Date April 25, 2018
Completion Date May 2021
Primary Completion Date July 2020
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Changes in net weight gain Baseline, 6 week, 12 week
Secondary Outcome
Measure Time Frame
Changes in body mass index (BMI) Baseline, 6 week, 12 week
Changes in waist circumference Baseline, 6 week, 12 week
Changes in blood pressure Baseline, 6 week, 12 week
Changes in triglycerides (TG) Baseline, 12 week
Changes in total cholesterol Baseline, 12 week
Changes in high-density lipoprotein (HDL) Baseline, 12 week
Changes in low-density lipoprotein (LDL) Baseline, 12 week
Changes in fasting glucose Baseline, 12 week
Changes in insulin Baseline, 12 week
Changes in insulin resistant index (IRI) Baseline, 12 week
Changes in positive and Negative Syndrome Scale (PANSS) Baseline, 6 week, 12 week
Changes in extrapyramidal Symptom Rating Scale (ESRS) Baseline, 6 week, 12 week
Changes in treatment Emergent Symptom Scale (TESS) Baseline, 6 week, 12 week
Enrollment 120
Condition
Intervention

Intervention Type: Drug

Intervention Name: Berberine

Description: Berberine tablets, 0.3g every time, two times daily

Arm Group Label: Berberine

Intervention Type: Drug

Intervention Name: Placebos

Description: Placebo tablets, 0.3g every time, two times daily

Arm Group Label: Placebo

Other Name: Placebo

Intervention Type: Drug

Intervention Name: Antipsychotic Agents

Description: Antipsychotic agents prescribed at the discretion of the patients' psychiatrists with respect to patients' conditions. Concomitant use of other psychotropic drugs will be generally allowed, including benzodiazepines and non-benzodiazepines insomnia and anti-anticholinergics for extrapyramidal symptoms, but anti-hyperlipidemic, antihypertensive and antidiabetic drugs will be not allowed. For those who have been under anti-hyperlipidemic, antihypertensive and antidiabetic treatment, they will be required to discontinue these treatments when they enter the trial.

Eligibility

Criteria:

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 one year;

- have a history of drug abuse in past one year;

- had an investigational drug treatment within the previous 6 months; or

- pregnant and lactation.

Gender: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Zhang-Jin ZHANG, MMed, PhD Principal Investigator School of Chinese Medicine, The University of Hong Kong
Overall Contact

Last Name: Zhang-Jin ZHANG, MMed, PhD

Phone: +852 3917 6445

Email: [email protected]

Location
Facility: Status: Contact: Investigator: Castle Peak Hospital - The Department of General Adult Psychiatry Wing-Him, Elvis LAI, MBBS +852 2456 7272 [email protected] Wing-Him, Elvis LAI, MBBS Sub-Investigator
Location Countries

Hong Kong

Verification Date

March 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: The University of Hong Kong

Investigator Full Name: Prof. Zhang Zhang-Jin

Investigator Title: Professor, Associate Director (Clinical Affairs)

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Berberine

Type: Active Comparator

Description: Patients will receive berberine pills in additional to current atypical antipsychotic agents

Label: Placebo

Type: Placebo Comparator

Description: Patients will receive placebos pills in additional to current atypical antipsychotic agents

Acronym BER
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov