Clinical trial NCT00302068: Exercise to Treat Depression in Individuals With Coronary Heart Disease
Official title: Understanding the Prognostic Benefits of Exercise and Anti-depressant Therapy (UPBEAT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depression
Heart Diseases
Keywords: Exercise
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2006-03-13
Enrollment: 101
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Some individuals with coronary heart disease (CHD) suffer from depression and use antidepressant medications to reduce symptoms. However, preliminary research has shown that exercise may be a more effective way to treat depression in these individuals. The purpose of this study is to evaluate the effects of exercise in reducing depression and improving heart function in individuals with CHD.

Detailed description: Coronary heart disease (CHD) is caused by a narrowing of the small blood vessels that supply blood and oxygen to the heart. It is the leading cause of death in the United States. Recent evidence has suggested that depression is a significant risk factor for individuals with CHD and may place additional strain on the heart. Selective serotonin reuptake inhibitors (SSRIs), a type of antidepressant medication, have been shown to be especially effective at reducing depression symptoms, particularly for individuals with CHD. However, many people fail to benefit from medication alone or they experience negative side effects. Therefore, a need exists to identify alternative approaches for treating depression in individuals with CHD. Preliminary research has shown that exercise may be an effective way to improve mood and treat depression. More research, however, is needed to confirm the benefits of exercise in individuals with CHD. The purpose of this study is to compare the effectiveness of a supervised exercise program, antidepressant treatment, and placebo in reducing depression and improving heart function in individuals with CHD.

This 16-week study will enroll adults with a history of CHD and depression. Participants will be randomly assigned to an aerobic exercise program, antidepressant medication, or placebo. At study entry, standardized psychological questionnaires will be completed and depression levels and exercise tolerance will be assessed. Participants' heart function will be evaluated through measures of flow-mediated vasodilatation, inflammation, platelet function, baroreflex, and heart rate variability. Participants assigned to the exercise program will be required to engage in structured aerobic exercise. Participants assigned to antidepressant medication will receive sertraline, an SSRI or placebo. The treating psychiatrist will be blinded to pill condition and will use supportive measures to help manage medication side effects. Outcome assessors will be unaware of patients' treatment assignments, and only the research pharmacist will be aware of which patients are assigned to sertraline or to placebo.

At Week 16, participants will return to the clinic for repeat assessments of baseline measures. A follow-up evaluation will occur six months following the end of treatment, and participants' depression levels and clinical status will be assessed.

Eligibility criteria: Inclusion Criteria:

* Persistent depressive symptoms that may include the following: depressed mood; diminished interest or pleasure in activities; change in appetite; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue or loss of energy; feelings of worthlessness or inappropriate guilt; diminished ability to think or concentrate; or recurrent thoughts of death or suicidal ideations
* Documented history of coronary heart disease (i.e., a prior heart attack, coronary artery bypass graft, or greater than 75% stenosis in at least one coronary artery)

Exclusion Criteria:

* Experienced an acute heart attack or any revascularization procedure (i.e., CABG or percutaneous transluminal coronary angioplasty) within 60 days of study entry
* Left ventricular ejection fraction \<30% with labile ECG changes prior to testing
* Currently using a pacemaker
* Resting blood pressure greater than 160/100 mmHg
* Left main disease \>50%
* Failure to meet our criteria for depression or achieve a score of ≥9 on the Beck Depression Inventory-II
* Any other concurrent psychiatric intervention
* Primary psychiatric diagnosis other than Major or Minor Depressive Episode
* Primary diagnosis of the following psychiatric disorders: schizophrenia, bipolar disorder, schizoaffective disorder, other psychotic disorder, dementia, current delirium, current obsessive compulsive disorder
* Experienced psychotic symptoms during the current depressive episode
* Current abuse or dependence on alcohol or other drugs
* Acute suicide risk
* Patients who, during the course of the study, would likely require treatment with additional psychotherapeutic agents
* Significant medical conditions that would make exercise or sertraline use medically inadvisable (e.g., unstable angina, heart attack within the 3 months prior to study entry, musculoskeletal problems, or congestive heart failure)
* Abnormal thyroid-stimulating hormone (TSH) level and glucose level greater than or equal to 126 mg/dL
* Patients who would not be able to be randomized to either the drug (e.g., adverse cardiac events such as prolonged QT interval, allergic responses) or exercise (e.g., musculoskeletal problems, abnormal cardiac response to exercise, such as exercise-induced VT, abnormal blood pressure response, etc.)
* Currently using medications that would make exercise or sertraline use medically inadvisable (e.g., clonidine, dicumarol, warfarin, anticonvulsants, or MAO inhibitors)
* Current uncontrolled medical condition that could be causing the depressive symptoms (e.g., thyroid dysfunction, anemia)
* Pregnant, planning to get pregnant during the study period, or lactating
* Herbal supplements with purported mood effects (e.g., St. John's wort, valerian, gingko)
* Current use of antidepressant medication
* Currently participating in psychotherapy
* Currently participating in regular aerobic exercise
* Documented failure to respond to sertraline therapy

Primary outcomes:
measure: Hamilton Depression Rating Scale
timeFrame: Measured at 16 weeks
Secondary outcomes:
measure: Heart Rate Variability (HRV)
timeFrame: Baseline, 16 weeks
measure: Percent Change in Flow Mediated Dilation (FMD)
timeFrame: Baseline, 16 weeks
measure: C-reactive Protein (CRP)
timeFrame: Baseline, 16 weeks
measure: Platelet Factor 4
timeFrame: Baseline, 16 weeks
measure: Baroreflex Sensitivity (BRS)
timeFrame: Baseline, 16 weeks
measure: Interleuken 6 (IL-6)
timeFrame: Baseline, 16 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: James A. Blumenthal, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Babyak M, Blumenthal JA, Herman S, Khatri P, Doraiswamy M, Moore K, Craighead WE, Baldewicz TT, Krishnan KR. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000 Sep-Oct;62(5):633-8. doi: 10.1097/00006842-200009000-00006.
citation: Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999 Oct 25;159(19):2349-56. doi: 10.1001/archinte.159.19.2349.
citation: Blumenthal JA, Sherwood A, Babyak MA, Watkins LL, Waugh R, Georgiades A, Bacon SL, Hayano J, Coleman RE, Hinderliter A. Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial. JAMA. 2005 Apr 6;293(13):1626-34. doi: 10.1001/jama.293.13.1626.
citation: Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. Exercise treatment for depression: efficacy and dose response. Am J Prev Med. 2005 Jan;28(1):1-8. doi: 10.1016/j.amepre.2004.09.003.
citation: Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression. Control Clin Trials. 2002 Oct;23(5):584-603. doi: 10.1016/s0197-2456(02)00226-x.
citation: Lett HS, Blumenthal JA, Babyak MA, Sherwood A, Strauman T, Robins C, Newman MF. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom Med. 2004 May-Jun;66(3):305-15. doi: 10.1097/01.psy.0000126207.43307.c0.
citation: Blumenthal JA, Sherwood A, Babyak MA, Watkins LL, Smith PJ, Hoffman BM, O'Hayer CV, Mabe S, Johnson J, Doraiswamy PM, Jiang W, Schocken DD, Hinderliter AL. Exercise and pharmacological treatment of depressive symptoms in patients with coronary heart disease: results from the UPBEAT (Understanding the Prognostic Benefits of Exercise and Antidepressant Therapy) study. J Am Coll Cardiol. 2012 Sep 18;60(12):1053-63. doi: 10.1016/j.jacc.2012.04.040. Epub 2012 Aug 1.