A Trial of Inflammatory Markers, Depressive Symptoms, and Heart Disease

NCT ID: NCT00208117

Last Updated: 2012-05-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2009-01-31

Brief Summary

The purpose of this study is to examine the relationship between depressive symptoms and markers of inflammation, two predictors of heart disease.

Detailed Description

Depressive symptoms and inflammatory markers have both been proposed as measures that indicate/precede coronary artery disease (CAD). However, no controlled research study has tested the impact of these two candidate CAD risk factors within the same design to see the directionality of their influence. This study will explore if simvastatin reduces depressive symptoms and if sertraline reduces C-Reactive protein (CRP). Additionally, the recruitment process will help determine the feasibility of a larger trial, powered for significance testing. Three hundred and seventy-five participants will be consented and screened for this study. We expect forty-two otherwise healthy outpatients to have both elevated symptoms and high CRP levels, and be willing to be randomly assigned to sertraline, an antidepressant, simvastatin, a drug with anti-inflammatory properties, or a placebo for 8 weeks. Depressive symptoms and inflammatory indicators will be assessed before treatment (screening and baseline), mid-treatment (after 4 weeks), post-treatment (after 8 weeks), and a follow-up visit (after 12 weeks), using blood tests and depression interviews. We expect that both inflammation and depressive symptoms may be reduced by both medications, but the number of subjects needed to test this hypothesis is not yet known. Hence, this pilot study will be conducted. Knowledge about the inter-dependency of these two CAD risk factors allows the most promising future observational/intervention studies to be designed and conducted.

Conditions

Depression; Coronary Artery Disease (CAD); Acute Coronary Syndrome (ACS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

1

Patients randomized to sertraline will receive 50 mg/d for the first 6 weeks. Based on clinical response and tolerability, the dosage will be increased to 2 tablets (100 mg/d) at the end of week 6 until the end of the study (8 weeks). If AEs occur, the dosage will be reduced by 50 mg (1 tablet) at a time, as long as a minimum daily dose of 50 mg is maintained. The psychiatry fellow will be responsible for drug administration and will see all patients weekly. All randomized patients will also be seen at the mid-treatment, post-treatment, and follow-up visits by the study psychiatrist to determine depression symptom severity (HAM-D), assess medical tolerance to the study medications, and ensure patient psychiatric safety. The study psychiatrist will be blinded to treatment allocation.

Group Type: ACTIVE_COMPARATOR

Sertraline (Zoloft)

Intervention Type: DRUG

Patients randomized to sertraline will receive 50 mg/d for the first 6 weeks. Based on clinical response and tolerability, the dosage will be increased to 2 tablets (100 mg/d) at the end of week 6 until the end of the study (8 weeks). If adverse events occur, the dosage will be reduced by 50 mg (1 tablet) at a time, as long as a minimum daily dose of 50 mg is maintained.

2

To ensure blinding of research assessments and the patient, all medications, including the placebo, will be reformulated into a matching number of identical-appearing pills. All randomized patients will also be seen at the mid-treatment, post-treatment, and follow-up visits by the study psychiatrist to determine depression symptom severity (HAM-D), assess the medical tolerance to the study medications (including placebo), and ensure patient psychiatric safety. The study psychiatrist will be blinded to treatment allocation.

Group Type: PLACEBO_COMPARATOR

Simvastatin (Zocor)

Intervention Type: DRUG

The placebo drug will be administered for 8 weeks. To ensure blinding of research assessments and the patient, all medications, including the placebo, will be reformulated into a matching number of identical-appearing pills.

Interventions

Sertraline (Zoloft)

Patients randomized to sertraline will receive 50 mg/d for the first 6 weeks. Based on clinical response and tolerability, the dosage will be increased to 2 tablets (100 mg/d) at the end of week 6 until the end of the study (8 weeks). If adverse events occur, the dosage will be reduced by 50 mg (1 tablet) at a time, as long as a minimum daily dose of 50 mg is maintained.

Intervention Type: DRUG

Simvastatin (Zocor)

The placebo drug will be administered for 8 weeks. To ensure blinding of research assessments and the patient, all medications, including the placebo, will be reformulated into a matching number of identical-appearing pills.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age 18 - 60

2. Mild depression

3. Inflammatory markers: CRP > 2

Exclusion Criteria

1. Non-English or Non-Spanish speakers

2. Active suicidal or homicidal ideation

3. Current alcohol or other substance abuse

4. Psychotic features

5. Current personality disorder

6. History of bipolar depressive disorder

7. Any current psychotic disorder

8. Current major depressive disorder

9. Current depression treatment or treatment within preceding 6 weeks

10. History of chronic liver and/or renal disease

11. Current use or contraindication to any of the tested medications

12. Absence of a response to a previous adequate trial of any of the tested medications

13. Pregnant or lactating women

14. History of coronary artery disease

15. Current use of statins

16. Current, regular aspirin use

17. Antibiotic use within the previous four weeks

18. History of diabetes

19. Inflammatory diseases

20. Meets NCEP guidelines for cholesterol lowering therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Alliance for Research on Schizophrenia and Depression

OTHER

Sponsor Role: collaborator

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karina W Davidson, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University: Behavioral Cardiovascular Health and Hypertension Program

Locations

Columbia University Department of General Medicine

New York, New York, United States

Countries

United States

Other Identifiers

4976 (Davidson)

Identifier Type: -

Identifier Source: org_study_id