Effects of Metformin and Fish Oil on Treatment With Clozapine

Phase 4

Terminated

• Conditions: Schizophrenia; Schizo-affective Disorder
• Interventions: Drug: Metformin; Drug: Fish Oil

• Registration Number: NCT02140788
• Lead Sponsor: Duke University

Brief Summary

One purpose of this study is to test whether adding metformin will limit some of the unwanted effects of clozapine, compared to not adding metformin. Metformin is a medication that is approved by the United States Food and Drug Administration (FDA) for the treatment of type-2 diabetes. Studies have found that people with type-2 diabetes often lose some weight when they take metformin, however the FDA has not approved metformin for weight loss, so for this study the use of metformin is investigational. This study will test whether metformin can help people with schizophrenia or schizoaffective disorders lose weight.

Another purpose of this study is to test whether adding fish oil will improve the benefit of clozapine and/or limit some of the unwanted effects of clozapine, compared to not adding fish oil. Fish oil is a medication used to reduce levels of some fats (triglycerides) in blood. Some studies have found that adding fish oil reduces psychosis (voices, suspiciousness). However the FDA has not approved fish oil for reducing psychosis, so for this study the use of fish oil is investigational. This study will test whether fish oil can help people with schizophrenia or schizoaffective disorders have less psychosis. Fish oil is not an antipsychotic medication.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2014-05
• Study First Submitted: 2014-05-14
• Study First Submitted QC: 2014-05-14
• Study First Posted: 2014-05-16
• Results First Submitted: 2014-11-06
• Results First Submitted QC: 2014-11-06
• Results First Posted: 2014-11-14
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-26

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• male or female patients with clinical diagnoses of schizophrenia or schizo-affective disorder
• between 18 and 60 years of age
• patients whose treating clinicians have recommended treatment with clozapine (and the patients have agreed and provided signed informed consent for treatment with clozapine)

Exclusion Criteria

• patients who have contraindications to metformin use, such as:

  • a diagnosis of congestive heart failure
  • renal impairment (serum creatinine > 1.5 in males; > 1.4 in females)
  • hepatic disease (AST or ALT > 2.0 times upper limit of normal (ULN)
  • positive hepatitis B surface antigen or hepatitis C antibody
  • total bilirubin>1.2x ULN; majority conjugated
  • metabolic acidosis (serum CO2 < lower limit of normal),
  • known hypersensitivity to metformin,
  • recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
  • alcohol abuse/dependence within the past month
  • concurrent treatment with drugs that are known to increase metformin blood levels including furosemide, nifedipine, and cationic drugs including cimetidine, amiloride, digoxin, morphine, procainamide, quinidine, ranitidine, triamterene, trimethoprim, and vancomycin

• patients with blood dyscrasias that could be worsened by added fish oil

• women who are pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Metformin and Fish Oil	Fish Oil	Subjects will continue to take the clozapine prescribed as standard of care. Subjects will receive Metformin and Fish Oil as part of the study.
Fish Oil	Fish Oil	Subjects will continue to take the clozapine prescribed as standard of care. Subjects assigned to added fish oil will receive OmegaBrite 500 mg gel cap BID days 1-7, and 1000 mg BID days 8-28 with breakfast and supper. Patients unable to tolerate the dose escalation to 1000 mg BID will have the fish oil dose reduce to 500 mg BID.
Metformin	Metformin	Subjects will continue to take the clozapine prescribed as standard of care. Subjects assigned to added metformin will receive metformin 250 mg BID days 1-3, 500 mg BID days 4-7, and 1000 mg BID days 8-28 with breakfast and supper. Patients unable to tolerate a dose escalation will have the metformin dose reduced to the previously tolerated lower dose.
Metformin and Fish Oil	Metformin	Subjects will continue to take the clozapine prescribed as standard of care. Subjects will receive Metformin and Fish Oil as part of the study.

Primary Outcome Measures

Name	Time	Method
Change in Weight	baseline, 2 weeks, 4 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in Fasting Levels of Non-HDL Cholesterol and Triglycerides	baseline, 2 weeks, 4 weeks
Changes in C-reactive Protein and Sedimentation Rates	baseline, 2 weeks, 4 weeks
Changes in Mole Percentages of Omega-3 PUFAs in Fasting Serum and RBC Membranes	baseline, 2 weeks, 4 weeks
Changes in Total Scores on the 4 Positive Brief Psychiatric Rating Scale (BPRS) Items	baseline, 2 weeks, 4 weeks	The four positive items are: Suspiciousness, Unusual Thought Content, Hallucinations, Conceptual Disorganization.