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

Phase 4

Completed

Interventions: Drug: Placebo
Drug: Telmisartan
Drug: Clozapine
Drug: Olanzapine

Brief Summary: 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: The specific aims include:

Primary Aims:

1. Examine the efficacy of telmisartan added to regular doses of clozapine or olanzapine in improving insulin resistance.

2. Examine the efficacy of telmisartan in reducing fasting triglycerides.

Secondary Aims:

1. Examine the effects of telmisartan on negative symptoms, positive symptoms, and cognitive function.

2. Examine telmisartan's effects on lipids, body composition, and waist/hip ratio.

3. Examine telmisartan's effects on inflammatory biomarkers including C-reactive protein (CRP) and interleukin 6 (IL-6).

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
B: Placebo	Placebo	(existing Clozapine or Olanzapine treatment) + (Placebo)
B: Placebo	Clozapine	(existing Clozapine or Olanzapine treatment) + (Placebo)
A: Telmisartan	Telmisartan	(existing Clozapine or Olanzapine treatment) + (Telmisartan)
A: Telmisartan	Clozapine	(existing Clozapine or Olanzapine treatment) + (Telmisartan)
A: Telmisartan	Olanzapine	(existing Clozapine or Olanzapine treatment) + (Telmisartan)
B: Placebo	Olanzapine	(existing Clozapine or Olanzapine treatment) + (Placebo)

Primary Outcome Measures

Name	Time	Method
Insulin Resistance	12 weeks	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.
Triglycerides	12 weeks	Fasting triglycerides assessed in both experimental and placebo arm at week 12.

Secondary Outcome Measures

Name	Time	Method
Lipid Metabolism - LDL-cholesterol and HDL-cholesterol	12 weeks	Lipid metabolism - fasting low density lipoprotein (LDL) and high density lipoprotein (HDL) are estimated in both experimental and placebo arms at 12 weeks.
Psychopathology - PANSS Total, PANSS - Negative Score, PANNS - Positive Score and SANS - Total Scores.	12 weeks	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.
Body Composition: Waist to Hip Ratio	12 weeks	Body composition as estimated by waist to hip ratio in both experimental and placebo arms at 12 weeks.
Body Composition: Percent Total Body Fat	12 weeks	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.