Clinical trial NCT00981526: Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
Official title: Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: Schizophrenia
Cognition
Metabolism
Antipsychotics
Psychopathology
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2009-09-22
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Age 18-65 years
2. Diagnosis of schizophrenia, any subtype or schizoaffective disorder, any subtype
3. Treatment with clozapine or olanzapine for at least 6 months
4. Stable dose of antipsychotic agent for at least one month
5. Well establish compliance with out-patient medications
6. 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:

1. Inability to provide informed consent
2. Current substance abuse
3. Psychiatrically unstable
4. Significant medical illness including severe cardiovascular, hepatic, renal disease
5. Current insulin treatment of diabetes
6. History of immunosuppression
7. Current or recent radiation or chemotherapy treatment for cancer
8. Chronic use of steroids
9. Pregnancy or breast feeding
10. Use of diuretics, digoxin, warfarin because the possible drug-drug interaction of telmisartan

Primary outcomes:
measure: Insulin Resistance
timeFrame: 12 weeks
measure: Triglycerides
timeFrame: 12 weeks
Secondary outcomes:
measure: Lipid Metabolism - LDL-cholesterol and HDL-cholesterol
timeFrame: 12 weeks
measure: Psychopathology - PANSS Total, PANSS - Negative Score, PANNS - Positive Score and SANS - Total Scores.
timeFrame: 12 weeks
measure: Body Composition: Waist to Hip Ratio
timeFrame: 12 weeks
measure: Body Composition: Percent Total Body Fat
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
Study officials:
affiliation: UMass Medical School
name: Xiaoduo Fan, MD, MPH, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fan X, Copeland P, Nawras S, Harrington A, Freudenreich O, Goff DC, Henderson DC. Adjunctive telmisartan treatment on body metabolism in clozapine or olanzapine treated patients with schizophrenia: a randomized, double blind, placebo controlled trial. Psychopharmacology (Berl). 2019 Jun;236(6):1949-1957. doi: 10.1007/s00213-019-5181-z. Epub 2019 Feb 12.
citation: Fan X, Song X, Zhao M, Jarskog LF, Natarajan R, Shukair N, Freudenreich O, Henderson DC, Goff DC. The effect of adjunctive telmisartan treatment on psychopathology and cognition in patients with schizophrenia. Acta Psychiatr Scand. 2017 Nov;136(5):465-472. doi: 10.1111/acps.12799. Epub 2017 Aug 29.