Anti-INFLammatory to Address Mood and Endothelial Dysfunction (INFLAMED)
Condition: Major Depressive Disorder; Depression; Depressive Symptoms; Cardiovascular Disease (CVD); Coronary Artery Disease (CAD); Heart Disease
MeSH terms: Cardiovascular Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Heart Diseases; Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: Pentoxifylline; Placebo; Standard Treatment
Intervention description: Pentoxifylline 400 mg p.o. t.i.d. for 12 weeks; 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.; 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 MeSH terms: Pentoxifylline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 36.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: Major Depressive Disorder; Depression; Depressive Symptoms; Cardiovascular Disease (CVD); Coronary Artery Disease (CAD); Heart Disease; Endothelial Function; Inflammation

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.
    

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