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Antipsychotics and Blood Vessel Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jess G. Fiedorowicz, University of Iowa
ClinicalTrials.gov Identifier:
NCT00585273
First received: December 19, 2007
Last updated: December 2, 2015
Last verified: December 2015
  Purpose

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
Bipolar Disorder
Schizophrenia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Cardiovascular Complications of First-line, Second-generation Antipsychotics

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Flow-mediated dilation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    % dilation of the brachial artery in response to 5 minutes of ischemia

  • Forearm vascular resistance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    % dilation of forearm blood vessels in response to pharmacological challenge measured using plethysmography


Enrollment: 44
Study Start Date: September 2007
Study Completion Date: December 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Incident users of antipsychotics.
2
Non-users of antipsychotics

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
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.
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00585273

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

Responsible Party: Jess G. Fiedorowicz, Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT00585273     History of Changes
Other Study ID Numbers: 200703764  University of Iowa GCRC #0740 
Study First Received: December 19, 2007
Last Updated: December 2, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Schizophrenia
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

ClinicalTrials.gov processed this record on September 30, 2016