Berberine as Adjuvant Treatment for Schizophrenia Patients

NCT02983188 | Completed Phase 2

• 1 other identifier: UW 17-020
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

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).

Conditions

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Metabolic Syndrome x

Keywords

Schizophrenia; Berberine; Metabolic Syndrome; Chinese medicine; Herbal medicine

Outcome Measures

Primary Outcomes (1)

• Changes in net weight gain

  Assessments will be conducted at baseline and once every three weeks thereafter.

  Baseline, 3 week, 6 week, 9 week, 12 week

Secondary Outcomes (11)

• Changes in body mass index (BMI)

  Baseline, 3 week, 6 week, 9 week, 12 week

• Changes in waist circumference (WC)

  Baseline, 3 week, 6 week, 9 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

Study Arms (2)

Berberine

ACTIVE COMPARATOR

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

Drug: Berberine; Drug: Antipsychotic Agents

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos; Drug: Antipsychotic Agents

Interventions

Berberine DRUG

Berberine tablets, 0.3g every time, two times daily

Berberine

Placebos DRUG

Placebo tablets, 0.3g every time, two times daily

Also known as: Placebo

Placebo

Antipsychotic Agents DRUG

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.

Berberine; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Hong Kong: lead
• Queen Mary Hospital, Hong Kong: collaborator
• Kowloon Hospital, Hong Kong: collaborator
• Castle Peak Hospital: collaborator
• Zhejiang Provincial Tongde Hospital: collaborator

Study Sites (1)

Castle Peak Hospital - The Department of General Adult Psychiatry

Tuenmen, Hong Kong

Location

Related Publications (14)

• Kane JM. Pharmacologic treatment of schizophrenia. Biol Psychiatry. 1999 Nov 15;46(10):1396-408. doi: 10.1016/s0006-3223(99)00059-1.

  PMID: 10578454 BACKGROUND

• Bressington DT, Mui J, Cheung EF, Petch J, Clark AB, Gray R. The prevalence of metabolic syndrome amongst patients with severe mental illness in the community in Hong Kong--a cross sectional study. BMC Psychiatry. 2013 Mar 18;13:87. doi: 10.1186/1471-244X-13-87.

  PMID: 23506322 BACKGROUND

• Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015 Dec;243(2):449-61. doi: 10.1016/j.atherosclerosis.2015.09.032. Epub 2015 Sep 30.

  PMID: 26520899 BACKGROUND

• Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049. Epub 2014 Dec 10.

  PMID: 25498346 BACKGROUND

• Hu Y, Young AJ, Ehli EA, Nowotny D, Davies PS, Droke EA, Soundy TJ, Davies GE. Metformin and berberine prevent olanzapine-induced weight gain in rats. PLoS One. 2014 Mar 25;9(3):e93310. doi: 10.1371/journal.pone.0093310. eCollection 2014.

  PMID: 24667776 BACKGROUND

• Kulkarni SK, Dhir A. On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. 2008 Jul 28;589(1-3):163-72. doi: 10.1016/j.ejphar.2008.05.043. Epub 2008 Jun 3.

  PMID: 18585703 BACKGROUND

• Peng WH, Wu CR, Chen CS, Chen CF, Leu ZC, Hsieh MT. Anxiolytic effect of berberine on exploratory activity of the mouse in two experimental anxiety models: interaction with drugs acting at 5-HT receptors. Life Sci. 2004 Oct 1;75(20):2451-62. doi: 10.1016/j.lfs.2004.04.032.

  PMID: 15350820 BACKGROUND

• Kawano M, Takagi R, Kaneko A, Matsushita S. Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses. J Neuroimmunol. 2015 Dec 15;289:43-55. doi: 10.1016/j.jneuroim.2015.10.001. Epub 2015 Oct 14.

  PMID: 26616870 BACKGROUND

• Salehi S, Filtz TM. Berberine possesses muscarinic agonist-like properties in cultured rodent cardiomyocytes. Pharmacol Res. 2011 Apr;63(4):335-40. doi: 10.1016/j.phrs.2010.12.004. Epub 2010 Dec 17.

  PMID: 21168503 BACKGROUND

• Harsing LG Jr, Lonart G, Vizi SE. Berbanes: search for novel alpha-2 adrenoceptor antagonists. Pol J Pharmacol Pharm. 1988 Nov-Dec;40(6):697-708.

  PMID: 2908367 BACKGROUND

• Wang HH, Cai M, Wang HN, Chen YC, Zhang RG, Wang Y, McAlonan GM, Bai YH, Wu WJ, Guo L, Zhang YH, Tan QR, Zhang ZJ. An assessor-blinded, randomized comparison of efficacy and tolerability of switching from olanzapine to ziprasidone and the combination of both in schizophrenia spectrum disorders. J Psychiatr Res. 2017 Feb;85:59-65. doi: 10.1016/j.jpsychires.2016.11.002. Epub 2016 Nov 4.

  PMID: 27837658 BACKGROUND

• Haffner SM, Miettinen H, Stern MP. The homeostasis model in the San Antonio Heart Study. Diabetes Care. 1997 Jul;20(7):1087-92. doi: 10.2337/diacare.20.7.1087.

  PMID: 9203442 BACKGROUND

• Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

  PMID: 3616518 BACKGROUND

• Gharabawi GM, Bossie CA, Lasser RA, Turkoz I, Rodriguez S, Chouinard G. Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS): cross-scale comparison in assessing tardive dyskinesia. Schizophr Res. 2005 Sep 15;77(2-3):119-28. doi: 10.1016/j.schres.2005.03.008.

  PMID: 15913963 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Metabolic Syndrome

Interventions

Berberine; Antipsychotic Agents

Condition Hierarchy (Ancestors)

Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Psychotropic Drugs

Study Officials

• Zhang-Jin ZHANG, MMed, PhD

  School of Chinese Medicine, The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Associate Director (Clinical Affairs)

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 6, 2016
• Study Start: April 25, 2018
• Primary Completion: December 30, 2020
• Study Completion: January 4, 2021
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)