Clinical trial NCT02140788: Effects of Metformin and Fish Oil on Treatment With Clozapine
Official title: A Comparison Of The Effects Of Added Metformin (Versus No Added Metformin) On Psychopathology, Lipids, And Measures of Inflammation During The Initiation Or Re-Institution Of Treatment With Clozapine In Patients With Schizophrenia Or Schizoaffective Disorder
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Schizophrenia
Schizo-affective Disorder
Keywords: schizophrenia
schizo-affective disorder
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-05-16
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Weight
timeFrame: baseline, 2 weeks, 4 weeks
Secondary outcomes:
measure: Changes in Fasting Levels of Non-HDL Cholesterol and Triglycerides
timeFrame: baseline, 2 weeks, 4 weeks
measure: Changes in C-reactive Protein and Sedimentation Rates
timeFrame: baseline, 2 weeks, 4 weeks
measure: Changes in Mole Percentages of Omega-3 PUFAs in Fasting Serum and RBC Membranes
timeFrame: baseline, 2 weeks, 4 weeks
measure: Changes in Total Scores on the 4 Positive Brief Psychiatric Rating Scale (BPRS) Items
timeFrame: baseline, 2 weeks, 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Duke University
name: Joseph McEvoy, MD
role: PRINCIPAL_INVESTIGATOR
References: