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Berberine as Adjuvant Treatment for Schizophrenia Patients (BER)

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ClinicalTrials.gov Identifier: NCT02983188
Recruitment Status : Recruiting
First Posted : December 6, 2016
Last Update Posted : May 11, 2018
Sponsor:
Collaborators:
Queen Mary Hospital, Hong Kong
Kowloon Hospital, Hong Kong
Castle Peak Hospital
Zhejiang Provincial Tongde Hospital
Information provided by (Responsible Party):
Prof. Zhang Zhang-Jin, The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE November 29, 2016
First Posted Date  ICMJE December 6, 2016
Last Update Posted Date May 11, 2018
Actual Study Start Date  ICMJE April 25, 2018
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 5, 2016)
Changes in net weight gain [ Time Frame: Baseline, 6 week, 12 week ]
Assessments will be conducted at baseline and once every six weeks thereafter.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02983188 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2016)
  • Changes in body mass index (BMI) [ Time Frame: Baseline, 6 week, 12 week ]
    Assessments will be conducted at baseline and once every six weeks thereafter.
  • Changes in waist circumference [ Time Frame: Baseline, 6 week, 12 week ]
    Assessments will be conducted at baseline and once every six weeks thereafter.
  • Changes in blood pressure [ Time Frame: Baseline, 6 week, 12 week ]
    Assessments will be conducted at baseline and once every six weeks thereafter.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Changes in insulin [ Time Frame: Baseline, 12 week ]
    Insulin 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.
  • Changes in insulin resistant index (IRI) [ Time Frame: Baseline, 12 week ]
    Insulin resistant index (IRI) is calculated with the formula, IRI = fasting insulin (103 μIU/L) x fasting glucose (mg/dL)/404.45 (fasting insulin (103 μIU/L) x fasting glucose [mmol/L]/22.5) (Haffner, 1997), based on the fasting glucose and insulin levels measured at the corresponding time frames.
  • 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.
  • 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.
  • Changes in treatment Emergent Symptom Scale (TESS) [ Time Frame: Baseline, 6 week, 12 week ]
    Adverse events will be recorded using the Treatment Emergent Symptom Scale (TESS). Assessments will be conducted at baseline and once every six weeks thereafter.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Berberine as Adjuvant Treatment for Schizophrenia Patients
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled Trial of Berberine as an Adjuvant to Treat Antipsychotic-induced Metabolic Syndrome in Patients With Schizophrenia Spectrum Disorders
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Schizophrenia
  • Schizophrenia Spectrum and Other Psychotic Disorders
  • Metabolic Syndrome x
Intervention  ICMJE
  • Drug: Berberine
    Berberine tablets, 0.3g every time, two times daily
  • Drug: Placebos
    Placebo tablets, 0.3g every time, two times daily
    Other Name: Placebo
  • Drug: Antipsychotic Agents
    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.
Study Arms  ICMJE
  • Active Comparator: Berberine
    Patients will receive berberine pills in additional to current atypical antipsychotic agents
    Interventions:
    • Drug: Berberine
    • Drug: Antipsychotic Agents
  • Placebo Comparator: Placebo
    Patients will receive placebos pills in additional to current atypical antipsychotic agents
    Interventions:
    • Drug: Placebos
    • Drug: Antipsychotic Agents
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 5, 2016)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zhang-Jin ZHANG, MMed, PhD +852 3917 6445 zhangzj@hku.hk
Contact: Marksman MAN, BCM BSc, PhD +852 3917 6466 marksman@hku.hk
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02983188
Other Study ID Numbers  ICMJE UW 17-020
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Prof. Zhang Zhang-Jin, The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE
  • Queen Mary Hospital, Hong Kong
  • Kowloon Hospital, Hong Kong
  • Castle Peak Hospital
  • Zhejiang Provincial Tongde Hospital
Investigators  ICMJE
Principal Investigator: Zhang-Jin ZHANG, MMed, PhD School of Chinese Medicine, The University of Hong Kong
PRS Account The University of Hong Kong
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP