Exercise to Treat Depression in Individuals With Coronary Heart Disease

Understanding the Prognostic Benefits of Exercise and Anti-depressant Therapy (UPBEAT)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00302068

Acronym

UPBEAT

Enrollment

101

Registered

2006-03-13

Start date

2006-07-31

Completion date

2011-12-31

Last updated

2015-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depression, Heart Diseases

Keywords

Exercise

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.

Interventions

BEHAVIORALSupervised Aerobic Exercise

Supervised aerobic exercise, three times per week, for 16 weeks.

DRUGSertraline

Sertraline (Zoloft), daily, for 16 weeks.

DRUGPlacebo Pill.

Placebo pill, daily, for 16 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

35 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Hamilton Depression Rating Scale	Measured at 16 weeks	The Hamilton Depression Rating Scale ranges from 0 to 52, with lower scores reflecting lower levels of depression and higher scores greater severity of depression.

Secondary

Measure	Time frame	Description
Percent Change in Flow Mediated Dilation (FMD)	Baseline, 16 weeks	Endothelial function assessed by flow mediated dilation (FMD). Brachial artery FMD was assessed following overnight fasting. Longitudinal B-mode ultrasound images of the brachial artery, 4-6 cm proximal to the antecubital crease, were obtained using an Aeuson (Mountain View, California) Aspen ultrasoundplatformwith an 11MHZ linear array transducer. lmages were obtained after 10 min of supine relaxation and during reactive hyperemia, induced following in ation of a forearm pneumatic occlusion cuff to supra-systolic pressure (\ 200 mmHg) for 5 minutes. FMD was defined as the maximum percent change inarterial diameter relative to restingbaseline from 10-120 sec post-deflation of the occlusion cuff.
C-reactive Protein (CRP)	Baseline, 16 weeks	—
Heart Rate Variability (HRV)	Baseline, 16 weeks	HRV is the variation in the time interval between heart beats. ECG was recorded for 24 hours on a 3-channel digital compact ash Holter recorder. During the recording period, patients engaged in their normal patterns of activity. ECG data were downloaded and edited using the Pathfinder digital ambulatory ECG analyzer (DelMar Reynolds, lrvine, California) and HRV was estimated from the standard deviation of all normal R-R intervals (SDNN)
Baroreflex Sensitivity (BRS)	Baseline, 16 weeks	—
Interleuken 6 (IL-6)	Baseline, 16 weeks	—
Platelet Factor 4	Baseline, 16 weeks	—

Countries

United States

Participant flow

Recruitment details

Enrollment began in June 2006 and ended in September 2010. Participants were recruited from physician referrals, community-based screenings, and mass media advertisements.

Participants by arm

Arm	Count
Supervised Aerobic Exercise Patients will attend 3 supervised group aerobic exercise sessions per week for 16 weeks. On the basis of peak heart rate achieved during the initial treadmill test, patients are assigned training ranges equivalent to 70% to 85% maximal heart rate reserve. Each aerobic session will consist of 30 min of walking or jogging on a treadmill at an intensity that would maintain heart rate within the assigned training range.	37
Sertraline (Zoloft) Participants are given the selective serotonin reuptake inhibitor sertraline. Medications are taken once daily; the dosage depends on the clinical response, but usually, each patient will start at 50 mg (1 pill) of drug and progress up to 200 mg (4 pills), contingent on therapeutic response and the presence of side effects.	40
Placebo Control Participants are given a matching placebo. Medications are taken once daily; the dosage depends on the clinical response, but usually, each patient will start at 50 mg (1 pill) of placebo and progress up to 200 mg (4 pills), contingent on therapeutic response and the presence of side effects.	24
Total	101

Baseline characteristics

Characteristic	Sertraline (Zoloft)	Placebo Control	Supervised Aerobic Exercise	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	16 Participants	10 Participants	15 Participants	41 Participants
Age, Categorical Between 18 and 65 years	24 Participants	14 Participants	22 Participants	60 Participants
Age, Continuous	63.4 years STANDARD_DEVIATION 10.2	63.5 years STANDARD_DEVIATION 11.4	64.7 years STANDARD_DEVIATION 11	63.9 years STANDARD_DEVIATION 11
Region of Enrollment United States	40 participants	24 participants	37 participants	101 participants
Sex: Female, Male Female	15 Participants	4 Participants	13 Participants	32 Participants
Sex: Female, Male Male	25 Participants	20 Participants	24 Participants	69 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 37	0 / 40	0 / 24
serious Total, serious adverse events	0 / 37	0 / 40	0 / 24

Outcome results

Primary

Hamilton Depression Rating Scale

The Hamilton Depression Rating Scale ranges from 0 to 52, with lower scores reflecting lower levels of depression and higher scores greater severity of depression.

Time frame: Measured at 16 weeks

Population: All completed subjects plus 1 subject in the sertraline arm who did not complete but provided assessment data.

Arm	Measure	Value (MEAN)
Supervised Aerobic Exercise	Hamilton Depression Rating Scale	-7.5 Raw changes in Ham-D scores
Sertraline (Zoloft)	Hamilton Depression Rating Scale	-6.1 Raw changes in Ham-D scores
Placebo Control	Hamilton Depression Rating Scale	-4.5 Raw changes in Ham-D scores

Secondary