Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)

Obesity Clinical Trial

— SECRET-II  

Official title:

Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02636439
• Other study ID #: IRB00032364
• Secondary ID: R01AG018915
• Status: Completed
• Phase: N/A
• Start date: August 2015
• Est. completion date: July 21, 2021

Study information

• Verified date: December 2020
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 88
• Est. completion date: July 21, 2021
• Est. primary completion date: July 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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 -

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic
• Obesity

Intervention

Behavioral:
• dietary, aerobic and resistance training
hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.
• dietary, and aerobic exercise
hypocaloric diet individual prescription for aerobic training.

Locations

Country	Name	City	State
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mitochondrial Content	Porin citrate synthase pre and post intervention.	20 weeks
Other	Mitochondrial Function	respiratory control ratio and mitofusin 2 concentration.pre and post intervention.	20 weeks
Primary	Peak Exercise Oxygen Consumption (VO2)	Peak exercise oxygen consumption (VO2) pre and post intervention	20 weeks
Secondary	Skeletal Muscle Mass	Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention.	20 weeks
Secondary	Thigh Skeletal Muscle Mass	Measure skeletal muscle mass by MRI analysis pre and post intervention.	20 weeks
Secondary	Thigh Muscle Composition	MRI skeletal muscle to intermuscular fat ratio	20 weeks
Secondary	Muscle Strength	maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)	20 weeks
Secondary	Muscle Quality	knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).	20 weeks
Secondary	Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score	The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.	20 weeks
Secondary	Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36)	The SF-36 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.	20 weeks