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

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

Detailed Description
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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.

Official Title
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A Randomized Controlled Trial of Inflammatory Markers, Depressive Symptoms, and Heart Disease

Conditions
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Depression, Coronary Artery Disease (CAD), Acute Coronary Syndrome (ACS)

Intervention / Treatment
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* Drug: Sertraline (Zoloft)
* Drug: Simvastatin (Zocor)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>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)<br>* 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.<br>|
| Placebo Comparator: 2<br>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)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on Beck Depression Inventory and C-Reactive Protein Level at weeks 4, 8, and 12 |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, inflammation, heart disease, randomized clinical trial, sertraline, simvastatin, placebo