Clinical trial NCT02983188: Berberine as Adjuvant Treatment for Schizophrenia Patients
Official title: A Double-blind, Randomized, Placebo-controlled Trial of Berberine as an Adjuvant to Treat Antipsychotic-induced Metabolic Syndrome in Patients With Schizophrenia Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Metabolic Syndrome x
Keywords: Schizophrenia
Berberine
Metabolic Syndrome
Chinese medicine
Herbal medicine
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: Kowloon Hospital, Hong Kong
name: Castle Peak Hospital
name: Zhejiang Provincial Tongde Hospital
First posted: 2016-12-06
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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, 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).

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.

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 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.

Primary outcomes:
measure: Changes in net weight gain
timeFrame: Baseline, 3 week, 6 week, 9 week, 12 week
Secondary outcomes:
measure: Changes in body mass index (BMI)
timeFrame: Baseline, 3 week, 6 week, 9 week, 12 week
measure: Changes in waist circumference (WC)
timeFrame: Baseline, 3 week, 6 week, 9 week, 12 week
measure: Changes in blood pressure
timeFrame: Baseline, 6 week, 12 week
measure: Changes in triglycerides (TG)
timeFrame: Baseline, 12 week
measure: Changes in total cholesterol
timeFrame: Baseline, 12 week
measure: Changes in high-density lipoprotein (HDL)
timeFrame: Baseline, 12 week
measure: Changes in low-density lipoprotein (LDL)
timeFrame: Baseline, 12 week
measure: Changes in fasting glucose
timeFrame: Baseline, 12 week
measure: Changes in glycated haemoglobin (HbA1c)
timeFrame: Baseline, 12 week
measure: Changes in positive and Negative Syndrome Scale (PANSS)
timeFrame: Baseline, 6 week, 12 week
measure: Changes in extrapyramidal Symptom Rating Scale (ESRS)
timeFrame: Baseline, 6 week, 12 week
Other outcomes:
Locations:
city: Tuen Mun
country: Hong Kong
facility: Castle Peak Hospital - The Department of General Adult Psychiatry
Study officials:
affiliation: School of Chinese Medicine, The University of Hong Kong
name: Zhang-Jin ZHANG, MMed, PhD
role: PRINCIPAL_INVESTIGATOR
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