Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia

Study Overview
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Brief Summary
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This is a 12-week, randomized, double-blinded, placebo-controlled trial of telmisartan 80 mg/day as an adjunctive to clozapine or olanzapine therapy, in 70 schizophrenia subjects to examine telmisartan's effect on glucose metabolism, weight, food intake, resting energy expenditure, and body composition. In addition, the study will examine insulin's effects on psychopathology and cognition. Potential subjects will be identified by their clinicians at the Freedom Trail Clinic, or Massachusetts General Hospital. Approximately 70 subjects will be enrolled.

Detailed Description
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The specific aims include: Primary Aims: Examine the efficacy of telmisartan added to regular doses of clozapine or olanzapine in improving insulin resistance. Examine the efficacy of telmisartan in reducing fasting triglycerides. Secondary Aims: Examine the effects of telmisartan on negative symptoms, positive symptoms, and cognitive function. Examine telmisartan's effects on lipids, body composition, and waist/hip ratio. Examine telmisartan's effects on inflammatory biomarkers including C-reactive protein (CRP) and interleukin 6 (IL-6).

Official Title
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Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Drug: Telmisartan
* Drug: Placebo
* Drug: Clozapine
* Drug: Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype Treatment with clozapine or olanzapine for at least 6 months Stable dose of antipsychotic agent for at least one month Well establish compliance with out-patient medications Females subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods (complete abstinence from sexual intercourse, female sterilization, sterilization of male partner, implants of levonorgestrel, injectable progestogen, oral contraceptives, intrauterine devices, or double barrier methods of contraception using spermicide with either a condom or diaphragm) during the study. Exclusion Criteria: Inability to provide informed consent Current substance abuse Psychiatrically unstable Significant medical illness including severe cardiovascular, hepatic, renal disease Current insulin treatment of diabetes History of immunosuppression Current or recent radiation or chemotherapy treatment for cancer Chronic use of steroids Pregnancy or breast feeding Use of diuretics, digoxin, warfarin because the possible drug-drug interaction of telmisartan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Telmisartan<br>(existing Clozapine or Olanzapine treatment) + (Telmisartan) | Drug: Telmisartan<br>* Telmisartan 40mg/day for the first 2 weeks. Telmisartan 80mg/day for the next 10 weeks.<br>Drug: Clozapine<br>* Clozapine (plus telmisartan or placebo) for 12 weeks.<br>Drug: Olanzapine<br>* Olanzapine (plus telmisartan or placebo) for 12 weeks.<br>|
| Placebo Comparator: B: Placebo<br>(existing Clozapine or Olanzapine treatment) + (Placebo) | Drug: Placebo<br>* Placebo (plus existing clozapine or olanzapine treatment) for 12 weeks.<br>Drug: Clozapine<br>* Clozapine (plus telmisartan or placebo) for 12 weeks.<br>Drug: Olanzapine<br>* Olanzapine (plus telmisartan or placebo) for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Resistance | Insulin resistance as estimated by homeostasis model of assessment of insulin resistance (HOMA-IR) at week 12 in both the experimental and placebo arm. Insulin resistance is a condition in which cells fail to respond to the normal action of the hormone in the body. The HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. The higher the score, the higher the level of insulin resistance. | 12 weeks | 
| Triglycerides | Fasting triglycerides assessed in both experimental and placebo arm at week 12. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid Metabolism - LDL-cholesterol and HDL-cholesterol | Lipid metabolism - fasting low density lipoprotein (LDL) and high density lipoprotein (HDL) are estimated in both experimental and placebo arms at 12 weeks. | 12 weeks | 
| Psychopathology - PANSS Total, PANSS - Negative Score, PANNS - Positive Score and SANS - Total Scores. | The Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) were used to assess the positive and negative symptoms in experimental and placebo arms at 12 weeks. The PANSS total scale includes positive and negative subscales. For both subscales, the score ranges from 7-49 and total PANSS score ranges from 30-210. The total scale is a summation of all the subscales. The SANS score ranges from 0-100. For all scales, a greater score represents a worse outcome. | 12 weeks | 
| Body Composition: Waist to Hip Ratio | Body composition as estimated by waist to hip ratio in both experimental and placebo arms at 12 weeks. | 12 weeks | 
| Body Composition: Percent Total Body Fat | Body composition estimated by percent total body fat as measured by a dual energy absorptiometry (DXA) scan in both experimental and placebo arms at 12 weeks. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology