Anti-INFLammatory to Address Mood and Endothelial Dysfunction (INFLAMED)
| Status: | Completed |
|---|---|
| Conditions: | Depression, Peripheral Vascular Disease, Major Depression Disorder (MDD), Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 40 - Any |
| Updated: | 4/21/2016 |
| Start Date: | June 2012 |
| End Date: | May 2014 |
Targeting Systemic Inflammation to Concurrently Treat Late-Life Depression and Reduce Coronary Artery Disease Risk
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.
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.
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.
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.
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
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