SchizophreniaPhase 4NCT00981526
Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
A Phase 4 study testing Telmisartan, Clozapine and Olanzapine in people with Schizophrenia and Schizoaffective Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- Telmisartan, Clozapine and Olanzapine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2009to May 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Massachusetts Medical School
Worcester, Massachusetts, 01605
About this study
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.
Read the 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).
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- Telmisartan, Placebo, Clozapine, Olanzapine
- Keywords
- Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TelmisartanDrug
Telmisartan 40mg/day for the first 2 weeks.
Telmisartan 80mg/day for the next 10 weeks.
PlaceboDrug
Placebo (plus existing clozapine or olanzapine treatment) for 12 weeks.
ClozapineDrug
Clozapine (plus telmisartan or placebo) for 12 weeks.
OlanzapineDrug
Olanzapine (plus telmisartan or placebo) for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| A: Telmisartan | Experimental | (existing Clozapine or Olanzapine treatment) + (Telmisartan) Receives: Drug: Telmisartan; Drug: Clozapine; Drug: Olanzapine |
| B: Placebo | Placebo comparator | (existing Clozapine or Olanzapine treatment) + (Placebo) Receives: Drug: Placebo; Drug: Clozapine; Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Triglycerides
Fasting triglycerides assessed in both experimental and placebo arm at week 12.
Measured: 12 weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2009 (estimated)
- Study startMar 2009
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Xiaoduo Fan, University of Massachusetts, Worcester
- Investigators
- Xiaoduo Fan, MD, MPH, MS, Principal investigator, UMass Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981526
- Sponsor's protocol ID
- 2008-P-000790
- Status last verified
- May 2018
- First submitted
- 18 Sep 2009
- Last updated
- 19 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30747254Fan 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.
PubMed 28851055
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Telmisartan as an Adjunctive Treatment for Metabolic Problems in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT00981526
- Acronym / sponsor ID
- 2008-P-000790
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- Schizophrenia, Cognition, Metabolism, Antipsychotics, Psychopathology
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Mar 2009
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 22 Sep 2009 (estimated)
- Results
- Posted 19 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Telmisartan | Experimental | Drug: Telmisartan, Drug: Clozapine, Drug: Olanzapine(existing Clozapine or Olanzapine treatment) + (Telmisartan) |
| B: Placebo | Placebo comparator | Drug: Placebo, Drug: Clozapine, Drug: Olanzapine(existing Clozapine or Olanzapine treatment) + (Placebo) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- Inability to provide informed consent
- Current substance abuse
- Psychiatrically unstable
- Significant medical illness including severe cardiovascular, hepatic, renal disease
- Current insulin treatment of diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TelmisartanTelmisartan 40mg/day for the first 2 weeks. Telmisartan 80mg/day for the next 10 weeks. | Drug | A: Telmisartan |
| PlaceboPlacebo (plus existing clozapine or olanzapine treatment) for 12 weeks. | Drug | B: Placebo |
| ClozapineClozapine (plus telmisartan or placebo) for 12 weeks. | Drug | A: Telmisartan, B: Placebo |
| OlanzapineOlanzapine (plus telmisartan or placebo) for 12 weeks. | Drug | A: Telmisartan, B: Placebo |
Primary outcome
Insulin Resistance
Time frame: 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
Time frame: 12 weeks
Fasting triglycerides assessed in both experimental and placebo arm at week 12.
4 secondary outcomes
Lipid Metabolism - LDL-cholesterol and HDL-cholesterol
Time frame: 12 weeks
Psychopathology - PANSS Total, PANSS - Negative Score, PANNS - Positive Score and SANS - Total Scores.
Time frame: 12 weeks
Body Composition: Waist to Hip Ratio
Time frame: 12 weeks
Body Composition: Percent Total Body Fat
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30747254Fan 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.
- Derived from this study: PubMed 28851055Fan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaoduo Fan, MD, MPH, MS principal investigator
UMass Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Telmisartan, Clozapine and Olanzapine in people with Schizophrenia and Schizoaffective Disorder, run by University of Massachusetts, Worcester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin Resistance (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00981526, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2018.