Study of the Effects of Caloric Restriction and Exercise Training (SECRET)
Leader: Dalane Kitzman, MD
Professor, Department of Internal Medicine
Section on Cardiology
NIH R37 AG018915/ 2009-2014
The primary aim of the study is to conduct a randomized, controlled, single-blinded, 2x2 design trial to examine weight loss via caloric restriction, aerobic exercise training, a combination of caloric restriction and exercise training, and attention control in 100 patients with heart failure and normal ejection fraction (HFNEF) and body mass index >30 in order to test the following hypotheses: 1)Both weight loss and exercise training will improve exercise intolerance and quality of life in older, obese patients with HFNEF. 2) Weight loss and exercise training combined will produce complementary effects on body and thigh muscle composition and additive improvements in exercise intolerance in patients with HFNEF. 3) Improvements in exercise tolerance will correlate with improvements in lean body mass, reversal of adverse thigh muscle remodeling, and increased thigh muscle capillarity.
Following baseline assessments, 100 patients with HFNEF aged > 60 years will be randomly assigned to 1 of the 4 arms: aerobic exercise training; caloric restriction; combined aerobic exercise training and caloric restriction; or attention control. Outcomes assessments will be performed at baseline and following the 20- week intervention. The primary outcomes will be peak exercise oxygen consumption (VO2peak) by expired gas analysis during graded treadmill exercise to exhaustion and quality of life by the Minnesota Living with Heart Failure Questionnaire (MLFH). Secondary, mechanistic outcomes, will include: total and regional lean and fat mass by DEXA; thigh skeletal muscle / intramuscular fat (SM/IMF) by MRI; skeletal muscle capillarity ratio, fiber type, and enzyme activity, on samples obtained by vastus lateralis needle biopsy; and circulating IL-6, CRP, and adiponectin. Personnel performing outcomes assessments will be blinded to treatment group. Clinical status, weight, and function will be checked at 12 month follow-up.