Antipsychotics and Blood Vessel Function

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00585273
Recruitment Status : Completed
First Posted : January 3, 2008
Last Update Posted : December 4, 2015
Information provided by (Responsible Party):
Jess G. Fiedorowicz, University of Iowa

Brief Summary:

Over the last decade, second generation antipsychotics have been increasingly utilized. Since their introduction, however, atypical antipsychotics have been increasingly associated with significant metabolic complications including hyperlipidemia, insulin resistance/diabetes mellitus, and obesity. These metabolic complications increase the risk for cardiovascular disease in populations with an already elevated risk.

The initial goal of the proposed study is to identify early signs of endothelial dysfunction and vascular disease in those treated with atypical antipsychotics. The identification of early signs of vascular disease may further link metabolic complications with any cardiovascular risk. Demonstration of changes in vascular function associated with atypical antipsychotics represents an important identifiable intermediate of more long-term cardiovascular risk.

The second goal of the proposed study is to identify genetic factors that may be associated with the development of cardiovascular disease, which can later serve as a guide to predict risk. Accurate prediction of risk may facilitate the future development of an empirical, risk-based, individualized selection process for antipsychotic medications.

Aim 1: To quantify the role of antipsychotic-induced metabolic complications on the development of vascular disease using measures of endothelial function.

Hypothesis 1: Atypical antipsychotics will lead to greater impairments in endothelial function, evidenced by decreased flow-mediated dilation from baseline measures and compared with changes over time in controls. Medication-induced metabolic complications will be temporally associated with these impairments in endothelial function.

Aim 2: To investigate the role of candidate pharmacogenetic polymorphisms with cardiovascular and metabolic complications of atypical antipsychotics.

Hypothesis 2: Profiles of polymorphisms at receptors targeted by atypical antipsychotics will be associated with impaired cardiovascular function and metabolic complications.

Condition or disease
Bipolar Disorder Schizophrenia

Study Type : Observational
Actual Enrollment : 44 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiovascular Complications of First-line, Second-generation Antipsychotics
Study Start Date : September 2007
Actual Primary Completion Date : November 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Incident users of antipsychotics.
Non-users of antipsychotics

Primary Outcome Measures :
  1. Flow-mediated dilation [ Time Frame: 6 months ]
    % dilation of the brachial artery in response to 5 minutes of ischemia

  2. Forearm vascular resistance [ Time Frame: 6 months ]
    % dilation of forearm blood vessels in response to pharmacological challenge measured using plethysmography

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Thirty patients, 18 - 50 years of age, who are being started on a first-line, second-generation, antipsychotic associated with weight gain (risperidone, olanzapine, or quetiapine) for the treatment of an affective or psychotic disorder, will be invited to participate. Participants must not have taken any of these antipsychotics or clozapine in the preceding three months. Another twenty psychiatric controls not taking antipsychotic medications will also be enrolled. Statistically, controls will serve primarily to compare changes in flow-mediated dilation over time rather than for direct comparison of variables between groups. Participation will be voluntary and initiated upon clinician or self-referral.

Inclusion Criteria:

  • 18-50 years of age
  • Being started on a first-line, second-generation, antipsychotic associated with weight gain (risperidone, olanzapine, or quetiapine) for the treatment of an affective or psychotic disorder -OR- psychiatric controls not taking antipsychotic medications will also be enrolled

Exclusion Criteria:

  • Exclusion criteria will include the presence of any of the following: neoplasm, active thyroid disease (i.e. not euthyroid), pregnancy or planned pregnancy, diabetes mellitus, Raynaud's disease, anticoagulant therapy, or inability to provide informed consent. We will exclude participants who have started valproic acid derivatives in the preceding 6 months, given its association with insulin resistance and weight gain. Participants with active substance abuse or dependence will also be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00585273

United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
University of Iowa
Principal Investigator: Jess G Fiedorowicz, M.D., Ph.D. University of Iowa

Additional Information:
Responsible Party: Jess G. Fiedorowicz, Assistant Professor, University of Iowa Identifier: NCT00585273     History of Changes
Other Study ID Numbers: 200703764
University of Iowa GCRC #0740
First Posted: January 3, 2008    Key Record Dates
Last Update Posted: December 4, 2015
Last Verified: December 2015

Additional relevant MeSH terms:
Bipolar Disorder
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Bipolar and Related Disorders
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs