Decreasing Risk of Coronary Artery Disease in Schizophrenia by Omega-3 Fatty Acid Supplementation (CAD)

This study has been completed.
American Heart Association
VA Pittsburgh Healthcare System
Information provided by (Responsible Party):
University of Pittsburgh Identifier:
First received: September 9, 2005
Last updated: March 7, 2016
Last verified: March 2016
The purpose of this study is to determine whether the administration of omega-3 polyunsaturated fatty acids, particularly eicosapentaenoic acid (EPA), can be useful both to reduce coronary artery disease (CAD) risk and illness severity in clinically-stable patients with schizophrenia (or schizoaffective disorder), major depression or bipolar disorder (depressed phase) being treated with lipid lowering drugs (e.g., statins).

Condition Intervention Phase
Schizoaffective Disorder
Major Depression
Bipolar Disorder
Coronary Artery Disease
Drug: Eicosapentaenoic acid (omega-3 fatty acid)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CAD Risk in Schizophrenia: Effect of Omega-3 Fatty Acid Supplementation

Resource links provided by NLM:

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To assess whether EPA supplementation can lead to improvement in further reducing CAD risk profile [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To test whether EPA supplementation can simultaneously improve the psychiatric status of patients with schizophrenia [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]

Enrollment: 57
Study Start Date: September 2005
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Eicosapentaenoic acid (omega-3 fatty acid, 2 g in 4x500 mg softgels daily) + Antipsychotic drug (doctor's choice) treatment for baseline, 1 month, 2 months and 4 months duration.
Drug: Eicosapentaenoic acid (omega-3 fatty acid)
2 g of Eicosapentaenoic acid in 4 x 500 mg capsules daily for baseline, 1 month, 2 months and 4 months
Other Name: EPA
Placebo Comparator: 2
Placebo (soy bean oil, 2 g in 4x500 mg softgels daily) + Antipsychotic drug (doctor's choice) treatment for baseline, 1 month, 2 months and 4 months duration.
Drug: Placebo
2 g of Placebo (soy bean oil) in 4 x 500 mg capsules daily for baseline, 1 month, 2 months and 4 months
Other Name: Soy bean oil

Detailed Description:
We propose to study the effects of EPA (2 g of EPA in 4 x 500 mg capsules daily) compared to placebo supplementation in clinically-stable schizophrenic patients being treated with statins (n=30 each) for 4 months using a randomized, double-blind design. The National Cholesterol Education Program Adult Treatment Panel III guidelines will be used to select those patients with CAD risk to participate. Clinical assessments and comprehensive assessment of the risk for CAD, including plasma total, high-density lipoprotein (HDL)- (HDL2- and HDL3-), low-density lipoprotein (LDL)- (LDL-Real-, Lp(a)-, and IDL-), and VLDL- (VLDL1,2- and VLDL3-) cholesterol, plasma triglycerides, as well as plasma homocysteine and high sensitivity C-reactive protein, will be conducted at baseline, 1 month, 2 months and 4 months after supplementation. It is anticipated that patients who receive EPA supplementation will have significantly greater reduction in plasma triglycerides and LDL4-cholesterol, and increases in HDL2-cholesterol measures, as well as improvements in psychopathology severity than those patients receiving placebo. If indeed EPA is effective in decreasing the risk of CAD, any psychiatric benefits from EPA supplementation will be a further boon to the patients and the treatment team. A tremendous advantage to the clinical use of EPA includes low cost, no significant side effects, and ease of use.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients meeting Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) criteria for schizophrenia (or schizoaffective disorder), major depression, or bipolar (depressed phase) disorder who are treated with antipsychotic, antidepressant or antimanic drugs and a lipid-lowering drug (statin) for 2 months or longer will be screened to participate in the proposed project.
  • Based upon the CAD risk determinants (see below) and the National Cholesterol Education Program (NCEP) recommendation of goals for LDL-lowering therapy, the investigators will only enroll schizophrenic patients with baseline (before statin treatment) LDL-cholesterol exceeding:

    • 70 mg/dL having CAD and CAD risk equivalents, e.g., peripheral arterial disease, abdominal aortic aneurysm, symptomatic carotid artery disease, and diabetes, as well as multiple risk factors that confer a 10-year risk for CAD > 20%
    • 130 mg/dL having 2 or more risk factors; and
    • 160 mg/dL having less than 2 risk factors to participate in the EPA trial.

In addition, these CAD-risk patients have not reached the NCEP goal level within the past year following statin treatment.

  • Risk factors for CAD. The NCEP Expert Panel (NIH Publication No. 01-3670, May 2001) on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III or ATPIII) recognizes the following CAD risk factors:

    • being male, 45 years or older, or being female 55 years or older;
    • family history of premature CAD;
    • current cigarette smoking;
    • hypertension with 140/90 mmHg or greater; and
    • low HDL-cholesterol (less than 40 mg/dL).

Exclusion Criteria:

  • Patients with history of bleeding disorders, current drug or alcohol abuse (within one month), neurological disorders (including head injury with loss of consciousness for greater than 10 minutes), antisocial personality disorder, borderline personality disorder, or mental retardation as indicated in medical records
  • Patients who are pregnant (as determined by urine pregnancy test)
  • Patients who have already achieved their NCEP goal in terms of their lipid profile (as indicated in laboratory tests) will be excluded.
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Please refer to this study by its identifier: NCT00167310

United States, Pennsylvania
VA Pittsburgh Healthcare System (University Drive)
Pittsburgh, Pennsylvania, United States, 15240
Sponsors and Collaborators
University of Pittsburgh
American Heart Association
VA Pittsburgh Healthcare System
Principal Investigator: Jeffrey K Yao, Ph.D., FACB University of Pittsburgh and VA Pittsburgh Healthcare System
  More Information

Responsible Party: University of Pittsburgh Identifier: NCT00167310     History of Changes
Other Study ID Numbers: AHA 0455676U  VA IRB Protocol ID:02063 
Study First Received: September 9, 2005
Last Updated: March 7, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
Omega-3 fatty acids
Antipsychotic drug
Antidepressant drug
Antimanic drug
Double-blind method
Bipolar (depressed phase)

Additional relevant MeSH terms:
Bipolar Disorder
Coronary Artery Disease
Coronary Disease
Depressive Disorder, Major
Myocardial Ischemia
Psychotic Disorders
Arterial Occlusive Diseases
Bipolar and Related Disorders
Cardiovascular Diseases
Depressive Disorder
Heart Diseases
Mental Disorders
Mood Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Vascular Diseases
Antipsychotic Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents processed this record on May 30, 2016