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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
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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.
The specific aims include:
Primary Aims:
Secondary Aims:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A: Telmisartan | Experimental | (existing Clozapine or Olanzapine treatment) + (Telmisartan) |
|
| B: Placebo | Placebo Comparator | (existing Clozapine or Olanzapine treatment) + (Placebo) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Telmisartan | Drug | Telmisartan 40mg/day for the first 2 weeks. Telmisartan 80mg/day for the next 10 weeks. |
|
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Xiaoduo Fan, MD, MPH, MS | UMass Medical School | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Medical School | Worcester | Massachusetts | 01605 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30747254 | Derived | 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. | |
| 28851055 |
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A total of 66 subjects were screened, 4 of which were screen fails. 62 subjects were then enrolled. Prior to randomization, 8 subjects withdrew consent. 54 subjects were randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | A: Telmisartan | Telmisartan 80mg/day |
| FG001 | B: Placebo | Placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | A: Telmisartan | Telmisartan 80mg/day |
| BG001 | B: Placebo | Placebo Group |
| BG002 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | HOMA-IR scores | 12 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | A: Experimental | Telmisartan 80mg/day |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Xiaoduo Fan | UMass Medical School | 508-856-3881 | xiaoduo.fan@umassmed.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011618 | Psychotic Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000077333 | Telmisartan |
| D003024 | Clozapine |
| D000077152 | Olanzapine |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo | Drug | Placebo (plus existing clozapine or olanzapine treatment) for 12 weeks. |
|
| Clozapine | Drug | Clozapine (plus telmisartan or placebo) for 12 weeks. |
|
| Olanzapine | Drug | Olanzapine (plus telmisartan or placebo) for 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. |
| 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 |
| 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. |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Triglycerides | Fasting triglycerides assessed in both experimental and placebo arm at week 12. | Posted | Mean | Standard Deviation | mg/dl | 12 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | mg/dl | 12 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
|
|
| Secondary | Body Composition: Waist to Hip Ratio | Body composition as estimated by waist to hip ratio in both experimental and placebo arms at 12 weeks. | Posted | Mean | Standard Deviation | Ratio | 12 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | percentage of body fat | 12 weeks |
|
|
|
| 0 |
| 22 |
| 8 |
| 22 |
| EG001 | B: Placebo | Placebo Group | 0 | 22 | 2 | 22 |
| Dizziness | General disorders | Systematic Assessment |
|
| Chest pain | General disorders | Systematic Assessment |
|
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| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003984 | Dibenzazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| PANSS positive score |
|
| SANS total score |
|