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Anti-INFLammatory to Address Mood and Endothelial Dysfunction (INFLAMED)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT01625845
First received: June 19, 2012
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

The objective of this clinical trial is to evaluate whether an anti-inflammatory medication, pentoxifylline, reduces depressive symptoms and improves artery function. Participants in this trial will be older primary care patients (60 years and up) who are depressed but do not have a history of cardiovascular disease. Half of these patients will receive pentoxifylline, and half will receive placebo. In addition, participants in both arms will receive an evidence-based psychological treatment called Beating the Blues®, which is a computerized, cognitive behavioral treatment program for depression. The investigators will use questionnaires to assess change in depressive symptoms and an ultrasound test to measure change in artery function from pre- to post-treatment. It is hypothesized that patients who receive pentoxifylline will show greater improvements in both depression and artery function than patients who receive placebo.


Condition Intervention Phase
Major Depressive Disorder
Depression
Depressive Symptoms
Cardiovascular Disease (CVD)
Coronary Artery Disease (CAD)
Heart Disease
Drug: Pentoxifylline
Other: Placebo
Behavioral: Standard Treatment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeting Systemic Inflammation to Concurrently Treat Late-Life Depression and Reduce Coronary Artery Disease Risk

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Change in Brachial Flow-Mediated Dilation (FMD) at 12 weeks. [ Time Frame: 0, 6, and 12 weeks ] [ Designated as safety issue: No ]
    Patients will undergo ultrasound assessment of brachial FMD in accordance with established guidelines. After a 10-minute supine rest, high-resolution baseline images of the brachial artery will be obtained from 3 consecutive cardiac cycles. Next, the forearm cuff will be inflated to 250 mmHg for 5 minutes and then will be rapidly deflated. At 60 and 90 seconds post-deflation, images from 3 consecutive cardiac cycles will be acquired. FMD values will be computed as the % increase in brachial diameter at either 60 or 90 seconds after cuff deflation

  • Change in Depressive Symptoms Severity at 12 Weeks [ Time Frame: 0, 6, and 12 weeks ] [ Designated as safety issue: No ]
    Self-reported depressive symptom severity (SCL-20 score)


Secondary Outcome Measures:
  • Change in Circulating Markers of Systemic Inflammation at 12 Weeks [ Time Frame: 0, 6, and 12 weeks ] [ Designated as safety issue: No ]
    Circulating levels of the proinflammatory cytokines interleukin (IL)-1α, IL-1β, IL-1 receptor antagonist, IL-6, and tumor necrosis factor (TNF)-α; the anti-inflammatory cytokine IL-10; and the acute-phase reactant C-reactive protein (CRP)


Estimated Enrollment: 50
Study Start Date: June 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pentoxifylline + Standard Treatment

Pentoxifylline: Pentoxifylline is phosphodiesterase inhibitor that interferes with proinflammatory cytokine signaling and synthesis. Participants will be instructed to take pentoxifylline 400 mg p.o. t.i.d. for 12 weeks.

Standard Treatment: Beating the Blues (BtB) is a widely used, empirically supported, computer-based, CBT program for depression designed for use in primary care clinics. BtB utilizes an interactive, multimedia format to deliver and eight 50-minute, weekly therapy sessions.

Drug: Pentoxifylline
Pentoxifylline 400 mg p.o. t.i.d. for 12 weeks
Other Names:
  • Trental
  • Pentoxil
  • Pentopak
Behavioral: Standard Treatment
BtB is a widely used, empirically supported, computer-based, CBT program for depression designed for use in primary care clinics. BtB utilizes an interactive, multimedia format to deliver and eight 50-minute, weekly therapy sessions. General topics covered include identifying and challenging automatic thoughts, cognitive errors, core beliefs, and attributional styles; activity scheduling; problem solving; graded exposure; task breakdown; sleep management; and relapse prevention. In addition to session work, patients are assigned homeworks that are customized to their needs and reviewed at the start of each session. A progress report, including whether the patient is experiencing suicidal ideation, is generated at the end of each session.
Other Names:
  • Computer-Based Cognitive Behavioral Therapy (CBT)
  • Computer-Based Psychotherapy
Placebo Comparator: Placebo + Standard Treatment

Placebos: Placebo pills will match the study drug for color, taste, texture, size, and smell. Participants will receive the same instructions as those randomized to pentoxifylline.

Standard Treatment: Beating the Blues (BtB) is a widely used, empirically supported, computer-based, CBT program for depression designed for use in primary care clinics. BtB utilizes an interactive, multimedia format to deliver and eight 50-minute, weekly therapy sessions.

Other: Placebo
Placebo pills will match the study drug for color, taste, texture, size, and smell. Participants will receive the same instructions as those randomized to pentoxifylline.
Behavioral: Standard Treatment
BtB is a widely used, empirically supported, computer-based, CBT program for depression designed for use in primary care clinics. BtB utilizes an interactive, multimedia format to deliver and eight 50-minute, weekly therapy sessions. General topics covered include identifying and challenging automatic thoughts, cognitive errors, core beliefs, and attributional styles; activity scheduling; problem solving; graded exposure; task breakdown; sleep management; and relapse prevention. In addition to session work, patients are assigned homeworks that are customized to their needs and reviewed at the start of each session. A progress report, including whether the patient is experiencing suicidal ideation, is generated at the end of each session.
Other Names:
  • Computer-Based Cognitive Behavioral Therapy (CBT)
  • Computer-Based Psychotherapy

Detailed Description:

Cardiovascular disease is the leading cause of death, and depression is the leading cause of disability in the United States. Previous research suggests that systemic inflammation may play an important role in the development of both depression and cardiovascular disease. Therefore, Aim #1 of this study is to examine whether adding an anti-inflammatory medication (pentoxifylline) to standard depression treatment (cognitive-behavioral therapy) improves both depressive symptoms and endothelial dysfunction, a sign of early cardiovascular disease. Aim #2 is to evaluate candidate mediators of treatment effects by examining whether reductions in multiple markers of systemic inflammation account for treatment-related improvements in depressive symptoms and endothelial dysfunction. To achieve these aims, a clinical trial of older depressed primary care patients free of cardiovascular disease is being conducted. Patients will be randomized to one of two groups: a standard depression treatment (a cognitive-behavioral treatment program) plus pentoxifylline or standard depression treatment plus placebo. The treatment phase of the study will be 12 weeks. At baseline, 6 weeks, and 12 weeks, patients will undergo assessments of depressive symptoms, various inflammatory markers, and endothelial function. Our index of endothelial function is brachial artery flow-mediated dilation, a noninvasive measure of endothelial function. Demonstrating that medications targeting systemic inflammation are effective for concurrently treating late-life depression and reducing CAD risk would place anti-inflammatory approaches in the collection of depression treatment strategies, as well as CAD prevention strategies, of the primary care provider. This change to clinical practice should result in improved management of both late-life depression and cardiovascular risk, which in turn would reduce disability, CAD morbidity, and mortality among older adults.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Primary care patients
  • Age ≥ 40 years
  • Clinically significant depressive symptoms, defined as a PHQ-9 score ≥15
  • English speaking

Exclusion Criteria:

  • History of clinical cardiovascular disease
  • History of cardiac arrhythmias or cardiomyopathy
  • History of carotid bruits
  • History of certain chronic disorders (HIV/AIDS, kidney disease, liver disease, systemic inflammatory disease, or past-year cancer)
  • History of bleeding disorder, gastrointestinal ulceration or bleeding, cerebrovascular aneurysm or bleeding, or retinal hemorrhage
  • History of migraine headaches
  • History of Raynaud's phenomenon
  • History of bipolar disorder or psychosis
  • Current use of anticoagulants or vasodilators (Lipid-lowering antihypertensive medications are allowed.)
  • Current use of acetazolamide, anticonvulsants, or thyroid replacements
  • Current use of glucocorticoids - including topical, nasal, or oral steroids - or anabolic steroids (Physiologic testosterone replacement therapy is allowed.)
  • Current use of anti-inflammatory agents (including, but not limited to, plaquenil, infliximab, etanercept, mycophenolate mofetil, sirolimus, tacrolimus, cyclosporine, pentoxifylline, thalidomide)
  • Known allergy or intolerance to pentoxifylline or other methylxanthines, such as , theophylline, caffeine, theobromine
  • Known allergy or intolerance to nitroglycerin.
  • Severe cognitive impairment (≥3 errors on 6-item cognitive screen105)
  • Current alcohol use problem (≥2 on CAGE questionnaire106)
  • Very severe depressive symptoms, defined as a PHQ-9 score ≥24
  • Acute risk of suicide
  • Vision or hearing problems
  • Unable to lie flat for 30 minutes at a time
  • Therapy for acute infection or other serious medical illnesses within 14 days prior to the pre-treatment visit (Therapy for acute infection or other serious medical illnesses that overlaps with a main study visit will result in postponement of that study visit until the course of therapy is completed; postponement outside of the allowed study visit timeframe will result in study discontinuation.)
  • Creatinine clearance < 50mL/min using a serum creatinine level measured at the pre-treatment visit
  • Hemoglobin < 9.0mg/dL at the pre-treatment visit
  • Alanine aminotransferase (ALT) level or aspartate aminotransferase (AST) > 3 times ULN at the pre-treatment visit
  • Total bilirubin > 2.5 times ULN at the pre-treatment visit
  • Current evidence of abuse of prescription medications
  • Current evidence of illicit drug use
  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: NCT01625845

Locations
United States, Indiana
Indiana University-Purdue University Indianapolis (IUPUI)
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Investigators
Principal Investigator: Jesse C Stewart, PhD Indiana University School of Medicine
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT01625845     History of Changes
Other Study ID Numbers: 1110007119, R24MH080827, 1737
Study First Received: June 19, 2012
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Indiana University:
Major Depressive Disorder
Depression
Depressive Symptoms
Cardiovascular Disease (CVD)
Coronary Artery Disease (CAD)
Heart Disease
Endothelial Function
Inflammation

Additional relevant MeSH terms:
Cardiovascular Diseases
Coronary Artery Disease
Coronary Disease
Depression
Depressive Disorder
Depressive Disorder, Major
Heart Diseases
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Behavioral Symptoms
Mental Disorders
Mood Disorders
Vascular Diseases
Pentoxifylline
Antioxidants
Cardiovascular Agents
Enzyme Inhibitors
Free Radical Scavengers
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Protective Agents
Radiation-Protective Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 20, 2014