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

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02636439
Acronym
SECRET-II
Enrollment
88
Registered
2015-12-21
Start date
2015-08-31
Completion date
2021-07-21
Last updated
2022-07-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure, Diastolic, Obesity

Keywords

Diastolic heart failure, Heart Failure, Elderly, Obesity

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.

Interventions

BEHAVIORALdietary, aerobic and resistance training

hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.

BEHAVIORALdietary, and aerobic exercise

hypocaloric diet individual prescription for aerobic training.

Sponsors

National Institute on Aging (NIA)
CollaboratorNIH
Wake Forest University Health Sciences
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No

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 -

Design outcomes

Primary

MeasureTime frameDescription
Peak Exercise Oxygen Consumption (VO2)20 weeksPeak exercise oxygen consumption (VO2) pre and post intervention

Secondary

MeasureTime frameDescription
Muscle Quality20 weeksknee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).
Skeletal Muscle Mass20 weeksMeasure skeletal muscle mass in kg by DEXA analysis pre and post intervention.
Thigh Skeletal Muscle Mass20 weeksMeasure skeletal muscle mass by MRI analysis pre and post intervention.
Thigh Muscle Composition20 weeksMRI skeletal muscle to intermuscular fat ratio
Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score20 weeksThe 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.
Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36)20 weeksThe 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.
Muscle Strength20 weeksmaximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)

Other

MeasureTime frameDescription
Mitochondrial Content20 weeksPorin citrate synthase pre and post intervention.
Mitochondrial Function20 weeksrespiratory control ratio and mitofusin 2 concentration.pre and post intervention.

Countries

United States

Participant flow

Participants by arm

ArmCount
Dietary, and Aerobic Exercise
Intervention for diet-A hypocaloric diet will be developed to achieve a 2800 kcal/week deficit, which should produce about 0.4 kg (1 lb.) weight loss per week. Intervention for aerobic exercise-Based on initial evaluations and the stress testing results, (HR, VO2, RPE) an individual exercise prescription will be developed for aerobic training. dietary, and aerobic exercise: hypocaloric diet individual prescription for aerobic training.
44
Dietary, Aerobic and Resistance Training
Intervention for diet-A hypocaloric diet will be developed to achieve a 2800 kcal/week deficit, which should produce about 0.4 kg (1 lb.) weight loss per week. Intervention for aerobic exercise-Based on initial evaluations and the stress testing results, (HR, VO2, RPE) an individual exercise prescription will be developed for aerobic training. Intervention for resistance training- Additional weight resistant exercise will be added to this arm. 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.
44
Total88

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event22
Overall StudyLost to Follow-up10
Overall StudyNon-compliance11
Overall StudyPersonal reasons20

Baseline characteristics

CharacteristicDietary, Aerobic and Resistance TrainingDietary, and Aerobic ExerciseTotal
Age, Continuous69.7 years
STANDARD_DEVIATION 5.8
67.9 years
STANDARD_DEVIATION 5.4
68.8 years
STANDARD_DEVIATION 5.7
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
44 Participants44 Participants88 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Peak exercise oxygen consumption (VO2)1530 ml/min
STANDARD_DEVIATION 366
1529 ml/min
STANDARD_DEVIATION 375
1530 ml/min
STANDARD_DEVIATION 368
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
23 Participants24 Participants47 Participants
Race (NIH/OMB)
More than one race
1 Participants1 Participants2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
20 Participants19 Participants39 Participants
Region of Enrollment
United States
44 Participants44 Participants88 Participants
Sex: Female, Male
Female
38 Participants37 Participants75 Participants
Sex: Female, Male
Male
6 Participants7 Participants13 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 440 / 44
other
Total, other adverse events
24 / 4425 / 44
serious
Total, serious adverse events
6 / 446 / 44

Outcome results

Primary

Peak Exercise Oxygen Consumption (VO2)

Peak exercise oxygen consumption (VO2) pre and post intervention

Time frame: 20 weeks

Population: Analysis completed on all participants with peak VO2 obtained (n=77).

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExercisePeak Exercise Oxygen Consumption (VO2)1609 ml/minStandard Error 24
Dietary, Aerobic, and Resistance TrainingPeak Exercise Oxygen Consumption (VO2)1653 ml/minStandard Error 24
p-value: 0.2195% CI: [-25, 112]ANCOVA
Secondary

Muscle Quality

knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).

Time frame: 20 weeks

Population: Analysis completed on all participants with MRI and Biodex measurements.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseMuscle Quality0.90 Nm/cm^2Standard Error 0.02
Dietary, Aerobic, and Resistance TrainingMuscle Quality0.97 Nm/cm^2Standard Error 0.02
p-value: 0.04395% CI: [0, 0.13]ANCOVA
Secondary

Muscle Strength

maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)

Time frame: 20 weeks

Population: Analysis completed on all participants with Biodex measures.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseMuscle Strength97.5 NmStandard Error 2.3
Dietary, Aerobic, and Resistance TrainingMuscle Strength103.9 NmStandard Error 2.2
p-value: 0.05395% CI: [-0.1, 12.9]ANCOVA
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.

Time frame: 20 weeks

Population: Analysis completed on all participants with KCCQ assessment.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseQuality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score91 score on a scaleStandard Error 2
Dietary, Aerobic, and Resistance TrainingQuality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score87 score on a scaleStandard Error 2
p-value: 0.0795% CI: [-10, 0]ANCOVA
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.

Time frame: 20 weeks

Population: Analysis completed on all participants with SF-36 assessment.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseQuality of Life Measured by Short Form 36 Item Questionnaire (SF-36)47.4 score on a scaleStandard Error 1.4
Dietary, Aerobic, and Resistance TrainingQuality of Life Measured by Short Form 36 Item Questionnaire (SF-36)46.9 score on a scaleStandard Error 1.3
p-value: 0.7995% CI: [-4.4, 3.3]ANCOVA
Secondary

Skeletal Muscle Mass

Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention.

Time frame: 20 weeks

Population: Analysis completed on all participants with DEXA measurement (n=78).

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseSkeletal Muscle Mass49.4 kgStandard Error 0.3
Dietary, Aerobic, and Resistance TrainingSkeletal Muscle Mass49.4 kgStandard Error 0.3
p-value: 0.8695% CI: [-1, 0.8]ANCOVA
Secondary

Thigh Muscle Composition

MRI skeletal muscle to intermuscular fat ratio

Time frame: 20 weeks

Population: Analysis completed on all participants with MRI measurements.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseThigh Muscle Composition4.0 ratioStandard Error 0.1
Dietary, Aerobic, and Resistance TrainingThigh Muscle Composition4.0 ratioStandard Error 0.1
p-value: 0.8595% CI: [-0.3, 0.2]ANCOVA
Secondary

Thigh Skeletal Muscle Mass

Measure skeletal muscle mass by MRI analysis pre and post intervention.

Time frame: 20 weeks

Population: Analysis completed on all participants with thigh MRI.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Dietary, and Aerobic ExerciseThigh Skeletal Muscle Mass108.5 cm^2Standard Error 1.2
Dietary, Aerobic, and Resistance TrainingThigh Skeletal Muscle Mass108.9 cm^2Standard Error 1.1
p-value: 0.7795% CI: [-2.8, 3.8]ANCOVA
Other Pre-specified

Mitochondrial Content

Porin citrate synthase pre and post intervention.

Time frame: 20 weeks

Other Pre-specified

Mitochondrial Function

respiratory control ratio and mitofusin 2 concentration.pre and post intervention.

Time frame: 20 weeks

Source: ClinicalTrials.gov · Data processed: Feb 11, 2026