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

NCT ID: NCT01625845

Last Updated: 2015-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2014-05-31

Brief Summary

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.

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.

Conditions

Major Depressive Disorder; Depression; Depressive Symptoms; Cardiovascular Disease (CVD); Coronary Artery Disease (CAD); Heart Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Pentoxifylline

Intervention Type: DRUG

Pentoxifylline 400 mg p.o. t.i.d. for 12 weeks

Standard Treatment

Intervention Type: BEHAVIORAL

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Intervention Type: BEHAVIORAL

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.

Interventions

Pentoxifylline

Pentoxifylline 400 mg p.o. t.i.d. for 12 weeks

Intervention Type: DRUG

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.

Intervention Type: OTHER

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Trental; Pentoxil; Pentopak; Computer-Based Cognitive Behavioral Therapy (CBT); Computer-Based Psychotherapy

Eligibility 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesse C Stewart, PhD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

Indiana University-Purdue University Indianapolis (IUPUI)

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

R24MH080827

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1737

Identifier Type: OTHER

Identifier Source: secondary_id

1110007119

Identifier Type: -

Identifier Source: org_study_id