Clinical trial NCT00981253: Stress Management and Biomarkers of Risk in Cardiac Rehabilitation
Official title: Enhancing Standard Cardiac Rehabilitation With Stress Management Training in Patients With Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Heart Disease
Keywords: Stress Management Training
Cardiac Rehabilitation
Stress
Depression
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-09-22
Enrollment: 164
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: The purpose of this study is to assess the extent to which combining exercise and stress management training (SMT) is more effective at improving biomarkers in vulnerable cardiac patients compared to exercise-based cardiac rehabilitation alone.

Detailed description: Coronary heart disease (CHD) is the leading cause of death in the United States and in roughly half the cases its first clinical manifestations, myocardial infarction (MI) or sudden cardiac death (SCD), are fatal. There is considerable evidence that "stress" plays a significant and independent role in the occurrence of CHD and its complications. This evidence has provided the rationale for developing interventional strategies to reduce stress in susceptible individuals in order to modify the natural history of these clinical events. There are now promising data to suggest that stress management training (SMT) is one such approach, and that SMT can have beneficial effects on psychosocial and medical outcomes. However, many of the randomized clinical trials (RCTs) employing stress management approaches in CHD patients have had important methodological limitations and several of the larger RCTs have failed to demonstrate a benefit for SMT over usual care, raising questions about the value of SMT for patients with CHD. Reliance on "hard" clinical endpoints is problematic because studies require such large sample sizes that they are logistically difficult to conduct and are prohibitively expensive. The use of intermediate pathophysiologic endpoints that have been shown independently to be associated with increased risk represents a novel and exciting opportunity to examine the added value of SMT in exercise-based cardiac rehabilitation (CR) compared to CR without SMT on key biomarkers of risk in vulnerable CHD patients.

This 12-week study will enroll adults with stable CHD who are eligible for CR. Participants will be randomly assigned to either standard cardiac rehabilitation or standard cardiac rehabilitation enhanced with weekly SMT. Prior to randomization, medical screening, standardized psychosocial questionnaires, mental stress testing, assessment of diet and physical activity, and exercise testing will be conducted. Additional biomarkers of risk will be assessed through measures of flow-mediated vasodilation, inflammation, platelet function, stress hormones, baroreflex, and heart rate variability.

Participants assigned to CR alone will engage in supervised exercise routines 3 times per week. Participants will be encouraged to maintain consistent exercise duration and effort throughout each session. Participants assigned to CR enhanced with SMT will engage in standard exercise-based cardiac rehabilitation and also receive weekly group SMT. At the conclusion of the 12-week intervention, participants will return for repeat assessments of stress and biomarker measures. At 6 months, 12 months, and annually up to 4 years participants will be contacted for information regarding major adverse cardiovascular events, other medical events and medication use.

Additionally a group of age, gender, and disease matched cardiac patients referred to CR, during the same time interval, but who elected not to participate in CR will form a non-randomized comparison group for cardiac events.

Overall, 164 participants were consented for study participation at Duke University Medical Center. Of these, 151 participants were randomized to either Standard Cardiac Rehabilitation or Enhanced Cardiac Rehabilitation. Post-intervention assessments were completed on 145 participants; 151 participants were available for intention-to-treat analysis.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Coronary Heart Disease (CHD)
* Eligibility for Cardiac Rehabilitation (CR) in North Carolina
* Capacity to give informed consent and follow study procedures

Exclusion Criteria:

* Received heart transplant
* LVEF \< 30%
* Labile ECG changes prior to testing
* Currently using a pacemaker
* Resting BP \> 200/120 mm Hg
* Left main disease \> 50%
* Unable to comply with assessment procedures
* Unwilling or unable to be randomized to treatment groups
* Primary diagnosis of the following psychiatric disorders: schizophrenia, dementia, current delirium, or other psychotic disorder
* Current alcohol or substance abuse disorder
* Acute suicide risk
* Actively undergoing ongoing psychiatric treatment

Primary outcomes:
measure: Absolute Composite Stress Score
timeFrame: Baseline; 12 weeks
measure: Change From Baseline to 12 Weeks in Individual Scaled Scores
timeFrame: Baseline; 12 weeks
Secondary outcomes:
measure: Major Adverse Cardiovascular Events (MACE) - All Cause Death, MI, Cardiac Revascularization and Cardiovascular Hospitalization.
timeFrame: Baseline through Follow-up (median, 3.2 years)
measure: Change in High-sensitivity C-Reactive Protein
timeFrame: Baseline; 12 weeks
measure: Heart Rate Variability During Controlled Breathing (HRV-DB)
timeFrame: At 12 weeks
measure: Baroreflex Sensitivity
timeFrame: At 12 weeks
measure: Heart Rate Variability During Rest
timeFrame: At 12 weeks
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals - Meadowmont
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center - Center for Living
state: North Carolina
Study officials:
affiliation: Duke University
name: James A. Blumenthal, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Alan Hinderliter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blumenthal JA, Jiang W, Babyak MA, Krantz DS, Frid DJ, Coleman RE, Waugh R, Hanson M, Appelbaum M, O'Connor C, Morris JJ. Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms. Arch Intern Med. 1997 Oct 27;157(19):2213-23.
citation: Rees K, Bennett P, West R, Davey SG, Ebrahim S. Psychological interventions for coronary heart disease. Cochrane Database Syst Rev. 2004;(2):CD002902. doi: 10.1002/14651858.CD002902.pub2.
citation: Jones DA, West RR. Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial. BMJ. 1996 Dec 14;313(7071):1517-21. doi: 10.1136/bmj.313.7071.1517.
citation: Frasure-Smith N, Lesperance F, Prince RH, Verrier P, Garber RA, Juneau M, Wolfson C, Bourassa MG. Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction. Lancet. 1997 Aug 16;350(9076):473-9. doi: 10.1016/S0140-6736(97)02142-9.
citation: Balady GJ, Williams MA, Ades PA, Bittner V, Comoss P, Foody JM, Franklin B, Sanderson B, Southard D; American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Nursing; American Heart Association Council on Epidemiology and Prevention; American Heart Association Council on Nutrition, Physical Activity, and Metabolism; American Association of Cardiovascular and Pulmonary Rehabilitation. Core components of cardiac rehabilitation/secondary prevention programs: 2007 update: a scientific statement from the American Heart Association Exercise, Cardiac Rehabilitation, and Prevention Committee, the Council on Clinical Cardiology; the Councils on Cardiovascular Nursing, Epidemiology and Prevention, and Nutrition, Physical Activity, and Metabolism; and the American Association of Cardiovascular and Pulmonary Rehabilitation. Circulation. 2007 May 22;115(20):2675-82. doi: 10.1161/CIRCULATIONAHA.106.180945. Epub 2007 May 18.
citation: Ades PA. Cardiac rehabilitation and secondary prevention of coronary heart disease. N Engl J Med. 2001 Sep 20;345(12):892-902. doi: 10.1056/NEJMra001529. No abstract available.
citation: Wenger NK, Froelicher ES, Smith LK, Ades PA, Berra K, Blumenthal JA, Certo CM, Dattilo AM, Davis D, DeBusk RF, et al. Cardiac rehabilitation as secondary prevention. Agency for Health Care Policy and Research and National Heart, Lung, and Blood Institute. Clin Pract Guidel Quick Ref Guide Clin. 1995 Oct;(17):1-23.
citation: Blumenthal JA, Babyak M, Wei J, O'Connor C, Waugh R, Eisenstein E, Mark D, Sherwood A, Woodley PS, Irwin RJ, Reed G. Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men. Am J Cardiol. 2002 Jan 15;89(2):164-8. doi: 10.1016/s0002-9149(01)02194-4.
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: Blumenthal JA, Sherwood A, Smith PJ, Watkins L, Mabe S, Kraus WE, Ingle K, Miller P, Hinderliter A. Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized, Clinical Efficacy Trial. Circulation. 2016 Apr 5;133(14):1341-50. doi: 10.1161/CIRCULATIONAHA.115.018926. Epub 2016 Mar 21.