<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02983188</url>
  </required_header>
  <id_info>
    <org_study_id>UW 17-020</org_study_id>
    <nct_id>NCT02983188</nct_id>
  </id_info>
  <brief_title>Berberine as Adjuvant Treatment for Schizophrenia Patients</brief_title>
  <acronym>BER</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen Mary Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kowloon Hospital, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Castle Peak Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Zhejiang Provincial Tongde Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Hong Kong</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      One double-blind, randomized, placebo-controlled trial is designed to examine whether&#xD;
      berberine added to current antipsychotic drugs could produce significantly greater efficacy&#xD;
      in reducing atypical antipsychotic-induced metabolic syndrome. To achieve this objective, 120&#xD;
      patients with schizophrenia spectrum disorders (SSD) who have developed metabolic syndrome&#xD;
      will be recruited and randomly assigned to receive additional treatment with placebo (n = 60)&#xD;
      or berberine (n = 60, 0.6 g/day, 0.3 g, b.i.d.) for 12 weeks. The primary outcome is changes&#xD;
      in net weight gain; other outcomes include body mass index (BMI), waist circumference (WC),&#xD;
      blood pressure, triglycerides (TG), total cholesterol, high-density lipoprotein (HDL), and&#xD;
      low-density lipoprotein (LDL), fasting glucose, glycated haemoglobin (HbA1c).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Schizophrenia is a severe mental illness that affects about 1% of the worldwide population.&#xD;
      Most patients develop a chronic course with frequent relapses and exacerbation of symptoms&#xD;
      and required to have long-term treatment. Although antipsychotic therapy is the mainstay of&#xD;
      the management of schizophrenia, the treatment outcomes are often unsatisfactory, largely due&#xD;
      to adverse drug reactions. Metabolic syndrome is a highly prevalent side effect incurred in&#xD;
      antipsychotic therapy, with a prevalence of 35% in patients with severe mental illness in&#xD;
      Hong Kong. No effective therapies are available in treating antipsychotic-induced metabolic&#xD;
      syndrome, although some antidiabetic medications may have limited benefits in controlling&#xD;
      weight gain and increased glucose level.&#xD;
&#xD;
      Berberine is a natural plant alkaloid isolated from the Chinese herb, Coptis chinensis&#xD;
      (Huang-Lian), which is traditionally used for diarrhea caused by bacterial and viral&#xD;
      infections in clinical practice. Several lines of evidence suggest that berberine has body&#xD;
      weight-lowering, anti-diabetic, and anti-hyperlipidemic effects. One recent study has further&#xD;
      shown that the addition of berberine significantly prevented olanzapine (OLZ)-Induced weight&#xD;
      gain in rats and modulated the expression of multiple key genes that control energy&#xD;
      expenditure.&#xD;
&#xD;
      In addition to the peripheral effects, berberine also broadly modulates brain biogenic amines&#xD;
      and related receptors that are involved in the pathogenesis of antipsychotic-induced&#xD;
      metabolic syndrome. This suggests that it may be suitable for the treatment of&#xD;
      antipsychotic-induced metabolic disturbance.&#xD;
&#xD;
      Over the past decade, a number of studies have demonstrated comparable efficacy of berberine&#xD;
      as mono- and combination therapy in reducing metabolic symptoms, without serious side effect.&#xD;
      The efficacy of berberine also has been well confirmed in patients with gastrointestinal,&#xD;
      liver, heart, and ovary disease as well as in renal-transplant recipients and healthy&#xD;
      volunteers. It is well tolerated and only minor digestive reactions were observed, mainly&#xD;
      nausea, diarrhea, constipation, abdominal distension and pain.&#xD;
&#xD;
      The results obtained from the clinical and animal studies of the group strongly suggest the&#xD;
      promising effects of berberine against OLZ-induced weight gain, without changing&#xD;
      pharmacokinetic and pharmacodynamics profile of OLZ at peripheral and central levels. This&#xD;
      warrants further evaluation in a larger randomized controlled trial.&#xD;
&#xD;
      The working hypothesis of the proposed study is that berberine as an adjuvant can control&#xD;
      weight gain and other metabolic symptoms associated with antipsychotic therapy. To test this&#xD;
      hypothesis, a 12-week, double-blind, randomized, placebo-controlled trial will be conducted&#xD;
      in patients with schizophrenia spectrum disorders (SSD) to determine whether berberine&#xD;
      adjunctive treatment could limit weight gain and improve other anthropometric and metabolic&#xD;
      measures in patients with SSD who have developed metabolic syndrome.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 25, 2018</start_date>
  <completion_date type="Actual">January 4, 2021</completion_date>
  <primary_completion_date type="Actual">December 30, 2020</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in net weight gain</measure>
    <time_frame>Baseline, 3 week, 6 week, 9 week, 12 week</time_frame>
    <description>Assessments will be conducted at baseline and once every three weeks thereafter.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in body mass index (BMI)</measure>
    <time_frame>Baseline, 3 week, 6 week, 9 week, 12 week</time_frame>
    <description>Assessments will be conducted at baseline and once every three weeks thereafter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in waist circumference (WC)</measure>
    <time_frame>Baseline, 3 week, 6 week, 9 week, 12 week</time_frame>
    <description>Assessments will be conducted at baseline and once every three weeks thereafter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood pressure</measure>
    <time_frame>Baseline, 6 week, 12 week</time_frame>
    <description>Assessments will be conducted at baseline and once every six weeks thereafter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in triglycerides (TG)</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in total cholesterol</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in high-density lipoprotein (HDL)</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in low-density lipoprotein (LDL)</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fasting glucose</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glycated haemoglobin (HbA1c)</measure>
    <time_frame>Baseline, 12 week</time_frame>
    <description>Glycated haemoglobin (HbA1c) 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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in positive and Negative Syndrome Scale (PANSS)</measure>
    <time_frame>Baseline, 6 week, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in extrapyramidal Symptom Rating Scale (ESRS)</measure>
    <time_frame>Baseline, 6 week, 12 week</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">113</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizophrenia Spectrum and Other Psychotic Disorders</condition>
  <condition>Metabolic Syndrome x</condition>
  <arm_group>
    <arm_group_label>Berberine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive berberine pills in additional to current atypical antipsychotic agents</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will receive placebos pills in additional to current atypical antipsychotic agents</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Berberine</intervention_name>
    <description>Berberine tablets, 0.3g every time, two times daily</description>
    <arm_group_label>Berberine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Placebo tablets, 0.3g every time, two times daily</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antipsychotic Agents</intervention_name>
    <description>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.</description>
    <arm_group_label>Berberine</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a primary diagnosis of SSD, including schizophrenia, schizoaffective disorder,&#xD;
             schizophreniform disorder, and psychotic disorder not otherwise specified according to&#xD;
             the Classification of Mental and Behavior Disorders (10th version);&#xD;
&#xD;
          -  have been under atypical antipsychotic treatment for at least 3 months and current&#xD;
             conditions are stable, indicated by no difficulty to communicate with investigators&#xD;
             and give informed consent; and&#xD;
&#xD;
          -  have developed metabolic syndrome according to the International Diabetes Federation&#xD;
             criteria for metabolic syndrome in Asian/Chinese population.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  serious comorbid gastrointestinal or other unstable medical conditions;&#xD;
&#xD;
          -  have suicidal ideas or attempts or aggressive behavior;&#xD;
&#xD;
          -  have a history of alcohol abuse in the past 3 months;&#xD;
&#xD;
          -  have a history of drug abuse in past 3 months;&#xD;
&#xD;
          -  had an investigational drug treatment within the previous 6 months; or&#xD;
&#xD;
          -  pregnant and lactation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhang-Jin ZHANG, MMed, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>School of Chinese Medicine, The University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Castle Peak Hospital - The Department of General Adult Psychiatry</name>
      <address>
        <city>Tuen Mun</city>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <reference>
    <citation>Kane JM. Pharmacologic treatment of schizophrenia. Biol Psychiatry. 1999 Nov 15;46(10):1396-408. doi: 10.1016/s0006-3223(99)00059-1.</citation>
    <PMID>10578454</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>23506322</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>26520899</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>25498346</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24667776</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>18585703</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>15350820</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>26616870</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>21168503</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>2908367</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>27837658</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>9203442</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>3616518</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>15913963</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>January 18, 2021</last_update_submitted>
  <last_update_submitted_qc>January 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Prof. Zhang Zhang-Jin</investigator_full_name>
    <investigator_title>Professor, Associate Director (Clinical Affairs)</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Berberine</keyword>
  <keyword>Metabolic Syndrome</keyword>
  <keyword>Chinese medicine</keyword>
  <keyword>Herbal medicine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Schizophrenia Spectrum and Other Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antipsychotic Agents</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02983188
org study id: UW 17-020
nct id: NCT02983188
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in net weight gain
time frame: Baseline, 3 week, 6 week, 9 week, 12 week
description: Assessments will be conducted at baseline and once every three weeks thereafter.
measure: Changes in body mass index (BMI)
time frame: Baseline, 3 week, 6 week, 9 week, 12 week
description: Assessments will be conducted at baseline and once every three weeks thereafter.
measure: Changes in waist circumference (WC)
time frame: Baseline, 3 week, 6 week, 9 week, 12 week
description: Assessments will be conducted at baseline and once every three weeks thereafter.
measure: Changes in blood pressure
time frame: Baseline, 6 week, 12 week
description: Assessments will be conducted at baseline and once every six weeks thereafter.
measure: Changes in triglycerides (TG)
time frame: Baseline, 12 week
description: 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.
measure: Changes in total cholesterol
time frame: Baseline, 12 week
description: 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.
measure: Changes in high-density lipoprotein (HDL)
time frame: Baseline, 12 week
description: 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.
measure: Changes in low-density lipoprotein (LDL)
time frame: Baseline, 12 week
description: 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.
measure: Changes in fasting glucose
time frame: Baseline, 12 week
description: 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.
measure: Changes in glycated haemoglobin (HbA1c)
time frame: Baseline, 12 week
description: Glycated haemoglobin (HbA1c) 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.
measure: Changes in positive and Negative Syndrome Scale (PANSS)
time frame: Baseline, 6 week, 12 week
description: 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.
measure: Changes in extrapyramidal Symptom Rating Scale (ESRS)
time frame: Baseline, 6 week, 12 week
description: 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.
arm group label: Berberine
arm group type: Active Comparator
description: Patients will receive berberine pills in additional to current atypical antipsychotic agents
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients will receive placebos pills in additional to current atypical antipsychotic agents
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, 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.
arm group label: Berberine
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Zhang-Jin ZHANG, MMed, PhD
role: Principal Investigator
affiliation: School of Chinese Medicine, The University of Hong Kong
facility: 
country: Hong Kong
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PMID: 15913963
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)
mesh term: Metabolic Syndrome
mesh term: Syndrome
mesh term: Schizophrenia
mesh term: Psychotic Disorders
mesh term: Schizophrenia Spectrum and Other Psychotic Disorders
mesh term: Antipsychotic Agents
sharing ipd: No