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
Lead Sponsor: The University of Hong Kong
|Source||The University of Hong Kong|
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.
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.
|Start Date||April 25, 2018|
|Completion Date||May 2021|
|Primary Completion Date||July 2020|
|Phase||Phase 2/Phase 3|
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.
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.
- 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.
- 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.
Minimum Age: 18 Years
Maximum Age: 65 Years
Healthy Volunteers: No
Last Name: Zhang-Jin ZHANG, MMed, PhD
Phone: +852 3917 6445
Email: [email protected]
Type: Principal Investigator
Investigator Affiliation: The University of Hong Kong
Investigator Full Name: Prof. Zhang Zhang-Jin
Investigator Title: Professor, Associate Director (Clinical Affairs)
|Has Expanded Access||No|
|Number Of Arms||2|
Type: Active Comparator
Description: Patients will receive berberine pills in additional to current atypical antipsychotic agents
Type: Placebo Comparator
Description: Patients will receive placebos pills in additional to current atypical antipsychotic agents
|Study Design Info||
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)