Back to resultsTelmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
Primary Purpose
Schizophrenia, Schizoaffective Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Telmisartan
Placebo
Clozapine
Olanzapine
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology
Eligibility Criteria
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
Sites / Locations
- University of Massachusetts Medical School
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
A: Telmisartan
B: Placebo
Arm Description
(existing Clozapine or Olanzapine treatment) + (Telmisartan)
(existing Clozapine or Olanzapine treatment) + (Placebo)
Outcomes
Primary Outcome Measures
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.
Triglycerides
Fasting triglycerides assessed in both experimental and placebo arm at week 12.
Secondary Outcome Measures
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.
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.
Body Composition: Waist to Hip Ratio
Body composition as estimated by waist to hip ratio in both experimental and placebo arms at 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.
Full Information
NCT ID
NCT00981526
First Posted
September 18, 2009
Last Updated
May 21, 2018
Sponsor
University of Massachusetts, Worcester
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT00981526
Brief Title
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
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
May 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Massachusetts, Worcester
Collaborators
National Institutes of Health (NIH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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:
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
66 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A: Telmisartan
Arm Type
Experimental
Arm Description
(existing Clozapine or Olanzapine treatment) + (Telmisartan)
Arm Title
B: Placebo
Arm Type
Placebo Comparator
Arm Description
(existing Clozapine or Olanzapine treatment) + (Placebo)
Intervention Type
Drug
Intervention Name(s)
Telmisartan
Intervention Description
Telmisartan 40mg/day for the first 2 weeks.
Telmisartan 80mg/day for the next 10 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo (plus existing clozapine or olanzapine treatment) for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Clozapine
Intervention Description
Clozapine (plus telmisartan or placebo) for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Intervention Description
Olanzapine (plus telmisartan or placebo) for 12 weeks.
Primary Outcome Measure Information:
Title
Insulin Resistance
Description
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.
Time Frame
12 weeks
Title
Triglycerides
Description
Fasting triglycerides assessed in both experimental and placebo arm at week 12.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Lipid Metabolism - LDL-cholesterol and HDL-cholesterol
Description
Lipid metabolism - fasting low density lipoprotein (LDL) and high density lipoprotein (HDL) are estimated in both experimental and placebo arms at 12 weeks.
Time Frame
12 weeks
Title
Psychopathology - PANSS Total, PANSS - Negative Score, PANNS - Positive Score and SANS - Total Scores.
Description
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.
Time Frame
12 weeks
Title
Body Composition: Waist to Hip Ratio
Description
Body composition as estimated by waist to hip ratio in both experimental and placebo arms at 12 weeks.
Time Frame
12 weeks
Title
Body Composition: Percent Total Body Fat
Description
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.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaoduo Fan, MD, MPH, MS
Organizational Affiliation
UMass Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30747254
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.
Results Reference
derived
PubMed Identifier
28851055
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.
Results Reference
derived
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Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
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