A Trial of Inflammatory Markers, Depressive Symptoms, and Heart Disease - Full Text View

Sponsor:	Columbia University
Collaborator:	National Alliance for Research on Schizophrenia and Depression
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00208117

Purpose

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

Condition	Intervention	Phase
Depression Coronary Artery Disease (CAD) Acute Coronary Syndrome (ACS)	Drug: Sertraline (Zoloft) Drug: Simvastatin (Zocor)	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Randomized Controlled Trial of Inflammatory Markers, Depressive Symptoms, and Heart Disease

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Depression Heart Diseases

Drug Information available for: Sertraline hydrochloride Sertraline Simvastatin

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

Score on Beck Depression Inventory and C-Reactive Protein Level at weeks 4, 8, and 12 [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2005
Study Completion Date:	January 2009
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator 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.	Drug: 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.
2: Placebo Comparator 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.	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.

Arms

Assigned Interventions

1: Active Comparator

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.

Drug: 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.

2: Placebo Comparator

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.

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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Age 18 - 60
Mild depression
Inflammatory markers: CRP > 2

Exclusion Criteria:

Non-English or Non-Spanish speakers
Active suicidal or homicidal ideation
Current alcohol or other substance abuse
Psychotic features
Current personality disorder
History of bipolar depressive disorder
Any current psychotic disorder
Current major depressive disorder
Current depression treatment or treatment within preceding 6 weeks
History of chronic liver and/or renal disease
Current use or contraindication to any of the tested medications
Absence of a response to a previous adequate trial of any of the tested medications
Pregnant or lactating women
History of coronary artery disease
Current use of statins
Current, regular aspirin use
Antibiotic use within the previous four weeks
History of diabetes
Inflammatory diseases
Meets NCEP guidelines for cholesterol lowering therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00208117

Locations

United States, New York
Columbia University Department of General Medicine
New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

National Alliance for Research on Schizophrenia and Depression

Investigators

Principal Investigator:

Karina W Davidson, PhD

Columbia University: Behavioral Cardiovascular Health and Hypertension Program

More Information

No publications provided

Responsible Party:	Columbia University ( Karina W. Davidson/Associate Professor of Behavioral Medicine )
Study ID Numbers:	4976 - Davidson
Study First Received:	September 15, 2005
Last Updated:	February 2, 2009
ClinicalTrials.gov Identifier:	NCT00208117 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Columbia University:

depression
inflammation
heart disease
randomized clinical trial

sertraline
simvastatin
placebo

Additional relevant MeSH terms:

Antimetabolites
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Myocardial Ischemia
Physiological Effects of Drugs
Psychotropic Drugs
Arteriosclerosis
Pathologic Processes
Mental Disorders
Syndrome
Therapeutic Uses
Sertraline
Cardiovascular Diseases
Antidepressive Agents

Arterial Occlusive Diseases
Heart Diseases
Depression
Disease
Simvastatin
Antilipemic Agents
Vascular Diseases
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Depressive Disorder
Serotonin Uptake Inhibitors
Pharmacologic Actions
Behavioral Symptoms
Coronary Disease

ClinicalTrials.gov processed this record on February 08, 2010