Stress Management and Biomarkers of Risk in Cardiac Rehabilitation (ENHANCED)
|ClinicalTrials.gov Identifier: NCT00981253|
Recruitment Status : Completed
First Posted : September 22, 2009
Results First Posted : January 5, 2018
Last Update Posted : February 1, 2018
|Condition or disease||Intervention/treatment|
|Coronary Heart Disease||Behavioral: SMT-enhanced Cardiac Rehabilitation Behavioral: Standard Cardiac Rehabilitation|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||164 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Enhancing Standard Cardiac Rehabilitation With Stress Management Training in Patients With Heart Disease|
|Study Start Date :||September 2009|
|Primary Completion Date :||July 2014|
|Study Completion Date :||February 2016|
Experimental: SMT-enhanced Cardiac Rehabilitation
Standard exercise-based cardiac rehabilitation with weekly stress management training for 12 weeks.
Behavioral: SMT-enhanced Cardiac Rehabilitation
Standard exercise-based cardiac rehabilitation, three times per week, enhanced with weekly stress management training for 12 weeks.
Active Comparator: Standard Cardiac Rehabilitation
Standard cardiac rehabilitation consisting of supervised exercise for 12 weeks.
Behavioral: Standard Cardiac Rehabilitation
Supervised exercise, three times per week, for 12 weeks.
- Absolute Composite Stress Score [ Time Frame: Baseline; 12 weeks ]A global stress measure (mean rank), was the primary outcome combining the following components at baseline and following treatment: Beck Depression Inventory II, Spielberger Anxiety Inventory-State, General Health Questionnaire, PROMIS Anger Questionnaire, and Perceived Stress Scale. A range from 1 to 147 was present with higher scores suggestive of better function. The change in each individual scaled score is presented in primary outcome 2.
- Change From Baseline to 12 Weeks in Individual Scaled Scores [ Time Frame: Baseline; 12 weeks ]
Beck Depression Inventory II: 21-item scale used to measure depression. Scores range from 0 to 63, with higher scores suggesting greater depressive symptoms.
State-Trait Anxiety Inventory: 20-item scale which assess levels of state anxiety. Scores range from 20 to 80 with scores ≥40 suggesting clinically significant anxiety.
General Health Questionnaire:12-item measure of general distress. Scores range from 0 to 36, with higher scores indicating greater emotional distress.
Patient-Reported Outcomes Measurement Information System (PROMIS) Anger: 8-item scale which assesses anger. Scores range from 8 to 40, with higher scores indicating greater anger.
Perceived Stress Scale: 10-item measure of general distress and perceived ability to cope. Scores range from 0 to 40, higher scores indicate greater stress.
- Major Adverse Cardiovascular Events (MACE) - All Cause Death, MI, Cardiac Revascularization and Cardiovascular Hospitalization. [ Time Frame: Baseline through Follow-up (median, 3.2 years) ]Patients documented all medical encounters on an annual basis after enrollment. Medical records were reviewed, and events, categorized on the basis of American College of Cardiology/American Heart Association criteria. The following medical events were included: all-cause mortality, fatal and nonfatal myocardial infarction (MI), coronary or peripheral artery revascularization, stroke/transient ischemic attack, and unstable angina requiring hospitalization.
- Change in High-sensitivity C-Reactive Protein [ Time Frame: Baseline; 12 weeks ]High-sensitivity C-reactive protein was quantified by ELISA. Values >10 mg/L were truncated at 10 to account for acute inflammatory processes that may have skewed the distribution of this blood marker.
- Heart Rate Variability During Controlled Breathing (HRV-DB) [ Time Frame: At 12 weeks ]Heart rate variability was obtained from beat-to-beat heart rate. Heart rate was assessed from R-R interval changes elicited during a 100-second controlled breathing task.
- Baroreflex Sensitivity [ Time Frame: At 12 weeks ]Baroreflex sensitivity was obtained from beat-to-beat heart rate and blood pressure recorded from patients in the supine position with a Nexfin noninvasive blood pressure monitor.
- Heart Rate Variability During Rest [ Time Frame: At 12 weeks ]Heart rate variability was obtained from beat-to-beat heart rate. Heart rate was assessed from R-R interval changes elicited during 5 minutes of normal relaxed breathing
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00981253
|United States, North Carolina|
|University of North Carolina Hospitals - Meadowmont|
|Chapel Hill, North Carolina, United States, 27517|
|Duke University Medical Center - Center for Living|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||James A. Blumenthal, PhD||Duke University|
|Principal Investigator:||Alan Hinderliter, MD||University of North Carolina, Chapel Hill|