SECRET-II: Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02636439
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 88
• Location: 1
• Arms: 2
• Actual Duration (Months): 71.7
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Heart Failure, Diastolic; Obesity	Behavioral: dietary, aerobic and resistance training; Behavioral: dietary, and aerobic exercise	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Jul 21, 2021
• Actual Study Completion Date: Jul 21, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Behavioral: dietary, and aerobic exercise; hypocaloric diet individual prescription for aerobic training.
Active Comparator: 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.	Behavioral: dietary, aerobic and resistance training; hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.; Behavioral: dietary, and aerobic exercise; hypocaloric diet individual prescription for aerobic training.

Outcome Measures

Primary Outcome Measures

1. Peak Exercise Oxygen Consumption (VO2) [20 weeks]

   Peak exercise oxygen consumption (VO2) pre and post intervention

Secondary Outcome Measures

1. Skeletal Muscle Mass [20 weeks]

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

2. Thigh Skeletal Muscle Mass [20 weeks]

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

3. Thigh Muscle Composition [20 weeks]

   MRI skeletal muscle to intermuscular fat ratio

4. Muscle Strength [20 weeks]

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

5. Muscle Quality [20 weeks]

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

6. Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score [20 weeks]

   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.

7. Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36) [20 weeks]

   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.

Other Outcome Measures

1. Mitochondrial Content [20 weeks]

   Porin citrate synthase pre and post intervention.

2. Mitochondrial Function [20 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Dalane W Kitzman, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 2, 2022
• Informed Consent Form - May 31, 2019

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02636439
• Other Study ID Numbers: IRB00032364; R01AG018915
• First Posted: Dec 21, 2015
• Last Update Posted: Jul 15, 2022
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Diastolic heart failure; Heart Failure; Elderly; Obesity
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Diastolic

Study Results

Participant Flow

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	44	44
COMPLETED	38	41
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic and Resistance Training	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	44	44	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.9 (5.4)	69.7 (5.8)	68.8 (5.7)
Sex: Female, Male (Count of Participants)
Female	37 84.1%	38 86.4%	75 85.2%
Male	7 15.9%	6 13.6%	13 14.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	44 100%	44 100%	88 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	24 54.5%	23 52.3%	47 53.4%
White	19 43.2%	20 45.5%	39 44.3%
More than one race	1 2.3%	1 2.3%	2 2.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	44 100%	44 100%	88 100%
Peak exercise oxygen consumption (VO2) (ml/min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ml/min]	1529 (375)	1530 (366)	1530 (368)

Outcome Measures

1. Primary Outcome

Title	Peak Exercise Oxygen Consumption (VO2)
Description	Peak exercise oxygen consumption (VO2) pre and post intervention
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	38	39
Least Squares Mean (Standard Error) [ml/min]	1609 (24)	1653 (24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.21
	Comments
	Method	ANCOVA
	Comments	adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	44
	Confidence Interval	(2-Sided) 95%; -25 to 112
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Skeletal Muscle Mass
Description	Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	38	40
Least Squares Mean (Standard Error) [kg]	49.4 (0.3)	49.4 (0.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Thigh Skeletal Muscle Mass
Description	Measure skeletal muscle mass by MRI analysis pre and post intervention.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with thigh MRI.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	39	40
Least Squares Mean (Standard Error) [cm^2]	108.5 (1.2)	108.9 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -2.8 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Thigh Muscle Composition
Description	MRI skeletal muscle to intermuscular fat ratio
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with MRI measurements.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	39	40
Least Squares Mean (Standard Error) [ratio]	4.0 (0.1)	4.0 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.85
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Muscle Strength
Description	maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with Biodex measures.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	25	28
Least Squares Mean (Standard Error) [Nm]	97.5 (2.3)	103.9 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95%; -0.1 to 12.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Muscle Quality
Description	knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with MRI and Biodex measurements.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	25	27
Least Squares Mean (Standard Error) [Nm/cm^2]	0.90 (0.02)	0.97 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Description	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

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with KCCQ assessment.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	38	41
Least Squares Mean (Standard Error) [score on a scale]	91 (2)	87 (2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5
	Confidence Interval	(2-Sided) 95%; -10 to 0
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36)
Description	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

Outcome Measure Data

Analysis Population Description

Analysis completed on all participants with SF-36 assessment.

Arm/Group Title	Dietary, and Aerobic Exercise	Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.	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.
Measure Participants	37	40
Least Squares Mean (Standard Error) [score on a scale]	47.4 (1.4)	46.9 (1.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dietary, and Aerobic Exercise, Dietary, Aerobic, and Resistance Training
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	ANCOVA
	Comments	Adjusted for baseline value, age, and sex.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -4.4 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Other Pre-specified Outcome

Title	Mitochondrial Content
Description	Porin citrate synthase pre and post intervention.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Mitochondrial Function
Description	respiratory control ratio and mitofusin 2 concentration.pre and post intervention.
Time Frame	20 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	20 weeks
Arm/Group Title	Dietary, and Aerobic Exercise		Dietary, Aerobic, and Resistance Training
Arm/Group Description	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.		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.
All Cause Mortality
	Dietary, and Aerobic Exercise		Dietary, Aerobic, and Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/44 (0%)		0/44 (0%)
Serious Adverse Events
	Dietary, and Aerobic Exercise		Dietary, Aerobic, and Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/44 (13.6%)		6/44 (13.6%)
Cardiac disorders
Heart failure exacerbation	0/44 (0%)	0	1/44 (2.3%)	2
Gastrointestinal disorders
Rectal bleeding	1/44 (2.3%)	1	0/44 (0%)	0
Diverticulitis	1/44 (2.3%)	1	0/44 (0%)	0
General disorders
Atypical chest pain	1/44 (2.3%)	1	0/44 (0%)	0
Infections and infestations
Cellulitis	1/44 (2.3%)	1	1/44 (2.3%)	1
Injury, poisoning and procedural complications
Fall	1/44 (2.3%)	1	2/44 (4.5%)	2
Metabolism and nutrition disorders
Hypoglycemia	1/44 (2.3%)	1	0/44 (0%)	0
Musculoskeletal and connective tissue disorders
Spinal surgery	1/44 (2.3%)	1	0/44 (0%)	0
Renal and urinary disorders
Acute renal failure	0/44 (0%)	0	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/44 (0%)	0	1/44 (2.3%)	1
Other (Not Including Serious) Adverse Events
	Dietary, and Aerobic Exercise		Dietary, Aerobic, and Resistance Training
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/44 (54.5%)		25/44 (56.8%)
Cardiac disorders
atrial fibrillation	1/44 (2.3%)	1	1/44 (2.3%)	1
chest pain	2/44 (4.5%)	3	3/44 (6.8%)	3
heart failure exacerbation	1/44 (2.3%)	1	1/44 (2.3%)	1
Eye disorders
elevated ocular pressure	0/44 (0%)	0	1/44 (2.3%)	1
Gastrointestinal disorders
acute pancreatitis	1/44 (2.3%)	1	0/44 (0%)	0
diarrhea	1/44 (2.3%)	1	0/44 (0%)	0
esophageal spasm	1/44 (2.3%)	1	0/44 (0%)	0
vomitting	2/44 (4.5%)	2	0/44 (0%)	0
General disorders
non-cardiac chest pain	1/44 (2.3%)	1	0/44 (0%)	0
Infections and infestations
gastroenteritis	0/44 (0%)	0	1/44 (2.3%)	1
upper respiratory infection	1/44 (2.3%)	1	1/44 (2.3%)	2
Injury, poisoning and procedural complications
broken tooth	1/44 (2.3%)	1	0/44 (0%)	0
fall	6/44 (13.6%)	7	6/44 (13.6%)	7
finger laceration	0/44 (0%)	0	1/44 (2.3%)	1
Metabolism and nutrition disorders
hypoglycemia	0/44 (0%)	0	1/44 (2.3%)	2
Musculoskeletal and connective tissue disorders
back pain	6/44 (13.6%)	7	3/44 (6.8%)	3
bursitis	0/44 (0%)	0	2/44 (4.5%)	2
foot pain	2/44 (4.5%)	2	0/44 (0%)	0
knee pain	1/44 (2.3%)	1	6/44 (13.6%)	7
leg pain	1/44 (2.3%)	1	1/44 (2.3%)	2
muscle strain	1/44 (2.3%)	1	0/44 (0%)	0
neck pain	0/44 (0%)	0	1/44 (2.3%)	1
shoulder pain	0/44 (0%)	0	2/44 (4.5%)	2
hip pain	1/44 (2.3%)	1	0/44 (0%)	0
Nervous system disorders
headache	1/44 (2.3%)	1	0/44 (0%)	0
presyncope	4/44 (9.1%)	4	0/44 (0%)	0
dizziness	1/44 (2.3%)	1	0/44 (0%)	0
Renal and urinary disorders
urinary tract infections	0/44 (0%)	0	2/44 (4.5%)	2
Reproductive system and breast disorders
post-menopausal bleeding	1/44 (2.3%)	1	0/44 (0%)	0
Respiratory, thoracic and mediastinal disorders
COPD exacerbation	0/44 (0%)	0	1/44 (2.3%)	1
dyspnea	1/44 (2.3%)	1	1/44 (2.3%)	1
Skin and subcutaneous tissue disorders
Abscess	1/44 (2.3%)	1	0/44 (0%)	0
cellulitis	0/44 (0%)	0	1/44 (2.3%)	1
diabetic ulcer	0/44 (0%)	0	1/44 (2.3%)	1
rash	0/44 (0%)	0	1/44 (2.3%)	1
Vascular disorders
hypertension	1/44 (2.3%)	1	0/44 (0%)	0
hypotension	0/44 (0%)	0	1/44 (2.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.