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

NCT01625845 | Completed Phase 2 Results DMC

• 3 other identifiers: 1110007119R24MH0808271737
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Change in Brachial Flow-Mediated Dilation (FMD) From Pre- to Post- Treatment

  Patients underwent ultrasound assessment of brachial FMD in accordance with established guidelines at pre- (0 weeks) and post- (12 weeks) treatment. After a 10-minute supine rest, high-resolution baseline images of the brachial artery were obtained from 3 consecutive cardiac cycles. Next, the forearm cuff was inflated to 250 mmHg for 5 minutes and then was rapidly deflated. At 60 and 90 seconds post-deflation, images from 3 consecutive cardiac cycles were acquired. FMD values were computed as the % change in brachial diameter at either 60 or 90 seconds after cuff deflation

  0 and 12 weeks

• Change in Depressive Symptoms Severity (Hopkins Symptom Checklist Depression Scale; SCL-20) From Pre- to Post- Treatment

  Self-reported depressive symptom severity was measured at pre- (0 weeks) and post- (12 weeks) treatment visits by the 20 depression items from the Symptom Checklist 90 (Hopkins Symptom Checklist depression scale; SCL-20). Each item on the scale ranges from 0 (not at all) to 4 (extremely). Total scores are the average across all response items and range from 0 to 4 with higher scores indicating greater levels of depressive symptoms.

  0 and 12 weeks

Secondary Outcomes (5)

• Change in Circulating Tumor Necrosis Factor-Alpha (TNF-a) From Pre- to Post-Treatment

  0 and12 weeks

• Change in Circulating Interleukin-6 (IL-6) From Pre- to Post-Treatment

  0 and 12 weeks

• Change in Circulating Interleukin-10 (IL-10) From Pre- to Post-Treatment

  0 and 12 weeks

• Change in Interleukin-1ra (IL-1ra) From Pre- to Post-Treatment

  0 and 12 weeks

• Change in Circulating C-Reactive Protein (CRP) From Pre- to Post-Treatment

  0 and 12 weeks

Study Arms (2)

Pentoxifylline + Standard Treatment

EXPERIMENTAL

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; Behavioral: Standard Treatment

Placebo + Standard Treatment

PLACEBO COMPARATOR

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; Behavioral: Standard Treatment

Interventions

Pentoxifylline DRUG

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

Also known as: Trental, Pentoxil, Pentopak

Pentoxifylline + Standard Treatment

Placebo 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.

Placebo + Standard Treatment

Standard Treatment 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.

Also known as: Computer-Based Cognitive Behavioral Therapy (CBT), Computer-Based Psychotherapy

Pentoxifylline + Standard Treatment; Placebo + Standard Treatment

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Indiana University-Purdue University Indianapolis (IUPUI)

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Cardiovascular Diseases; Coronary Artery Disease; Heart Diseases; Inflammation

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Missing data precluded analysis of two secondary outcome variables: IL-1α and IL-1β. Due to the very small sample of randomized patients, conclusions should not be drawn from the results of this pilot trial.

Results Point of Contact

• Title: Jesse C. Stewart, Ph.D.
• Organization: Indiana University-Purdue University Indianapolis (IUPUI)

jstew@iupui.edu

(317) 274-6761

Study Officials

• Jesse C Stewart, PhD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: June 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: December 3, 2015
• Results First Posted: December 3, 2015

Record last verified: 2015-10

Locations

US (1)