Clinical trial NCT02636439: Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)
Official title: Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure, Diastolic
Obesity
Keywords: Diastolic heart failure
Heart Failure
Elderly
Obesity
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2015-12-21
Enrollment: 88
Sex: ALL
Minimum age (years): 60
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 examine the effects of weight loss via hypocaloric diet (CR)and aerobic exercise (AT) compared to the effects of weight loss via hypocaloric diet (CR), aerobic training (AT)and resistance training (RT).

Detailed description: Heart failure with preserved ejection fraction (HFPEF) is the most common form of HF, is nearly unique to the older population, particularly older women, and is increasing in prevalence. Exercise intolerance, with severe exertional dyspnea and fatigue, is the primary manifestation of chronic HFPEF and is a major determinant of these patients' severely reduced quality of life (QOL). However, its pathophysiology is poorly understood and its optimal treatment remains undefined.

Our recent data and others' indicate that in older HFPEF patients, both increased adiposity and abnormalities in skeletal muscle are major contributors to exercise intolerance and potential therapeutic targets. Obesity is one of the strongest risk factors for HFPEF, and is a robust predictor of physical disability in older persons. The investigator recently reported that in HFPEF compared to age-matched controls, percent total and leg lean mass are significantly reduced and independently predict exercise capacity.

Using MRI and needle biopsy of the thigh muscle, the investigators found increased fat infiltration, reduced capillary density and percent type I oxidative fibers, and trends for reduced muscle mitochondrial mass and function. Reduced exercise capacity was related to each of these muscle abnormalities, supporting their important role in HFPEF.

Diet, with or without aerobic exercise, can increase exercise capacity and quality of life in older obese persons with a variety of disorders, but usually results in significant loss of skeletal muscle mass, which could potentially have adverse long term consequences. The purpose of this trial is to determine if addition of resistance training to diet plus aerobic exercise training can improve skeletal muscle mass and function in HFPEF.

Multiple lines of evidence and our preliminary data indicate that resistance training (RT) may be an ideal addition to CR+AT for HFPEF, since RT reliably increases muscle mass, quality, strength, and function, significantly more than AT, and can prevent nearly 50% of the muscle mass loss during CR.

Therefore, the primary aim of the proposed study is to conduct a randomized, single-blinded 20-week intervention trial of RT added to CR+AT in 84 overweight / obese (BMI greater than 28 kg/m2), older (age greater than 60 years) HFPEF patients to test the following primary hypothesis:

The addition of resistance training to CR+AT will improve exercise capacity.

Eligibility criteria: Inclusion Criteria:

1. Age 60 years or older
2. Ejection fraction ≥ 50%
3. Left Ventricular Diastolic Dysfunction ≥ grade 1
4. BMI ≥ 28 kg/m2
5. HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score \>/= 3 or Rich et al. criteria for HF

Exclusion Criteria:

1. Valvular heart disease as the primary etiology of CHF (congestive heart failure)
2. Significant change in cardiac medication or Heart Failure symptoms \<6 weeks
3. Hospitalization or urgent care visit \<6 weeks
4. Uncontrolled hypertension
5. Uncontrolled diabetes
6. Evidence of significant Chronic Obstructive Pulmonary Disease (COPD)
7. Recent or debilitating stroke
8. Cancer or other noncardiovascular conditions with life expectancy less than 2 years
9. Significant anemia (\<10 g/dL Hgb)
10. Significant renal insufficiency (eGFR \<30 mL/min/1.73m2)
11. Pregnant or of child-bearing potential
12. Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder
13. Plans to leave area within the study period
14. Refuses informed consent -

Primary outcomes:
measure: Peak Exercise Oxygen Consumption (VO2)
timeFrame: 20 weeks
Secondary outcomes:
measure: Skeletal Muscle Mass
timeFrame: 20 weeks
measure: Thigh Skeletal Muscle Mass
timeFrame: 20 weeks
measure: Thigh Muscle Composition
timeFrame: 20 weeks
measure: Muscle Strength
timeFrame: 20 weeks
measure: Muscle Quality
timeFrame: 20 weeks
measure: Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
timeFrame: 20 weeks
measure: Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36)
timeFrame: 20 weeks
Other outcomes:
measure: Mitochondrial Content
timeFrame: 20 weeks
measure: Mitochondrial Function
timeFrame: 20 weeks
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Dalane W Kitzman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brubaker PH, Nicklas BJ, Houston DK, Hundley WG, Chen H, Molina AJA, Lyles WM, Nelson B, Upadhya B, Newland R, Kitzman DW. A Randomized, Controlled Trial of Resistance Training Added to Caloric Restriction Plus Aerobic Exercise Training in Obese Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2023 Feb;16(2):e010161. doi: 10.1161/CIRCHEARTFAILURE.122.010161. Epub 2022 Oct 31.