Stress Management and Biomarkers of Risk in Cardiac Rehabilitation (ENHANCED)

January 8, 2018 updated by: Duke University

Enhancing Standard Cardiac Rehabilitation With Stress Management Training in Patients With Heart Disease

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

164

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27517
        • University of North Carolina Hospitals - Meadowmont
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center - Center for Living

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline; 12 weeks
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.
Baseline; 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline through Follow-up (median, 3.2 years)
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.
Baseline; 12 weeks
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.
At 12 weeks
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.
At 12 weeks
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
At 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

  • Principal Investigator: James A. Blumenthal, PhD, Duke University
  • Principal Investigator: Alan Hinderliter, MD, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

February 1, 2016

Study Registration Dates

First Submitted

September 21, 2009

First Submitted That Met QC Criteria

September 21, 2009

First Posted (Estimate)

September 22, 2009

Study Record Updates

Last Update Posted (Actual)

February 1, 2018

Last Update Submitted That Met QC Criteria

January 8, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00015896
  • R01HL093374-01A2 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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