Effects of Metformin and Fish Oil on Treatment With Clozapine

NCT02140788 | Terminated Phase 4 Results

• 1 other identifier: Pro00027822
• Study Type: interventional
• Target: 34
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Schizophrenia; Schizo-affective Disorder

Keywords

schizophrenia; schizo-affective disorder

Outcome Measures

Primary Outcomes (1)

• Change in Weight

  baseline, 2 weeks, 4 weeks

Secondary Outcomes (4)

• 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

Study Arms (4)

Metformin

ACTIVE COMPARATOR

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.

Drug: Metformin

Fish Oil

ACTIVE COMPARATOR

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.

Drug: Fish Oil

Metformin and Fish Oil

ACTIVE COMPARATOR

Subjects will continue to take the clozapine prescribed as standard of care. Subjects will receive Metformin and Fish Oil as part of the study.

Drug: Metformin; Drug: Fish Oil

No medication added

NO INTERVENTION

Subjects will continue to take the clozapine prescribed as standard of care. Subjects will not receive Metformin or Fish Oil.

Interventions

Metformin DRUG

Metformin; Metformin and Fish Oil

Fish Oil DRUG

Fish Oil; Metformin and Fish Oil

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Metformin; Fish Oils

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Oils; Lipids

Limitations and Caveats

Patients were not randomized per protocol and the study was terminated. Data analysis was not performed.

Results Point of Contact

• Title: Joseph P. McEvoy
• Organization: Duke University Health System

JMCEVOY@gru.edu

919-819-9295

Study Officials

• Joseph McEvoy, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2014
• First Posted: May 16, 2014
• Study Start: May 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: October 26, 2023
• Results First Posted: November 14, 2014

Record last verified: 2014-05