Heart Failure, DiastolicSECRET-IINCT02636439
Exercise Intolerance in Elderly Patients With HFpEF(Heart Failure With Preserved Ejection Fraction)
A study testing dietary, aerobic and resistance training and dietary, and aerobic exercise in people with Heart Failure, Diastolic and Obesity, run by Wake Forest University Health Sciences at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Heart Failure, Diastolic, Obesity
- What is being tested?
- dietary, aerobic and resistance training and dietary, and aerobic exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2015to 21 Jul 2021
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 60 years or older
- Ejection fraction ≥ 50%
- Left Ventricular Diastolic Dysfunction ≥ grade 1
- BMI ≥ 28 kg/m2
- HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score >/= 3 or Rich et al. criteria for HF
Who cannot join
- Valvular heart disease as the primary etiology of CHF (congestive heart failure)
- Significant change in cardiac medication or Heart Failure symptoms <6 weeks
- Hospitalization or urgent care visit <6 weeks
- Uncontrolled hypertension
- Uncontrolled diabetes
- Evidence of significant Chronic Obstructive Pulmonary Disease (COPD)
Show all 14Show fewer
- Recent or debilitating stroke
- Cancer or other noncardiovascular conditions with life expectancy less than 2 years
- Significant anemia (<10 g/dL Hgb)
- Significant renal insufficiency (eGFR <30 mL/min/1.73m2)
- Pregnant or of child-bearing potential
- Psychiatric disease- uncontrolled major psychoses, depressions, dementia, or personality disorder
- Plans to leave area within the study period
- Refuses informed consent -
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official title: Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction
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).
Read the 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.
- Conditions
- Heart Failure, Diastolic, Obesity
- Being tested
- dietary, aerobic and resistance training, dietary, and aerobic exercise
- Keywords
- Diastolic heart failure, Heart Failure, Elderly, Obesity
- Medical subject headings
- Heart Failure, Diastolic, Obesity, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dietary, aerobic and resistance trainingBehavioural
hypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training.
dietary, and aerobic exerciseBehavioural
hypocaloric diet individual prescription for aerobic training.
| Study group | Role | What they receive |
|---|---|---|
| dietary, and aerobic exercise | Active comparator | 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. Receives: Behavioral: dietary, and aerobic exercise |
| dietary, aerobic and resistance training | Active comparator | 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. Receives: Behavioral: dietary, aerobic and resistance training; Behavioral: dietary, and aerobic exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Exercise Oxygen Consumption (VO2)
Peak exercise oxygen consumption (VO2) pre and post intervention
Measured: 20 weeks
Secondary outcomes (7)
Skeletal Muscle Mass
Measure skeletal muscle mass in kg by DEXA analysis pre and post intervention.
Measured: 20 weeks
Thigh Skeletal Muscle Mass
Measure skeletal muscle mass by MRI analysis pre and post intervention.
Measured: 20 weeks
Thigh Muscle Composition
MRI skeletal muscle to intermuscular fat ratio
Measured: 20 weeks
Muscle Strength
maximal isokinetic knee extensor strength (Newton-meters, Nm) using an isokinetic dynamometer (Biodex®)
Measured: 20 weeks
Muscle Quality
knee extensor strength to thigh muscle area assessed by MRI (Nm/cm2).
Measured: 20 weeks
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.
Measured: 20 weeks
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.
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2015 (estimated)
- Study startAug 2015
- Primary completion21 Jul 2021
- Study completion21 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Dalane W Kitzman, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02636439
- Sponsor's protocol ID
- IRB00032364
- Other IDs
- R01AG018915
- Acronym
- SECRET-II
- Status last verified
- Dec 2020
- First submitted
- 9 Dec 2015
- Last updated
- 15 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schaich CL, Hughes TM, Kitzman DW, Jung Y, Chen H, Nicklas BJ, Houston DK, Brubaker PH, Molina AJA, Hugenschmidt CE. Neurocognitive Impairments and Their Improvement Following Exercise and Dietary Interventions in Older Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2024 Jan;17(1):e011134. doi: 10.1161/CIRCHEARTFAILURE.123.011134. Epub 2023 Dec 1. No abstract available.
PubMed 38037817Brubaker 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.
PubMed 36314122
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effects Caloric Restriction and Exercise Training in Patients With Heart Failure and a Normal Ejection Fraction
- ClinicalTrials.gov ID
- NCT02636439
- Acronym / sponsor ID
- SECRET-II / IRB00032364
- Conditions
- Heart Failure, Diastolic, Obesity
- Keywords
- Diastolic heart failure, Heart Failure, Elderly, Obesity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Aug 2015 (actual)
- Primary completion
- 21 Jul 2021 (actual)
- Study completion
- 21 Jul 2021 (actual)
- First posted
- 21 Dec 2015 (estimated)
- Results
- Posted 15 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dietary, and aerobic exercise | Active comparator | Behavioral: dietary, and aerobic exerciseIntervention 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, aerobic and resistance training | Active comparator | Behavioral: dietary, aerobic and resistance training, Behavioral: dietary, and aerobic exerciseIntervention 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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 60 years or older
- Ejection fraction ≥ 50%
- Left Ventricular Diastolic Dysfunction ≥ grade 1
- BMI ≥ 28 kg/m2
- HF symptoms/ signs by cardiologist review, using NHANES HF Clinical Score >/= 3 or Rich et al. criteria for HF
Key exclusion criteria (14 listed)
- Valvular heart disease as the primary etiology of CHF (congestive heart failure)
- Significant change in cardiac medication or Heart Failure symptoms <6 weeks
- Hospitalization or urgent care visit <6 weeks
- Uncontrolled hypertension
- Uncontrolled diabetes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dietary, aerobic and resistance traininghypocaloric diet individual exercise prescription for aerobic training individual exercise prescription for resistance training. | Behavioural | dietary, aerobic and resistance training |
| dietary, and aerobic exercisehypocaloric diet individual prescription for aerobic training. | Behavioural | dietary, aerobic and resistance training, dietary, and aerobic exercise |
Primary outcome
Peak Exercise Oxygen Consumption (VO2)
Time frame: 20 weeks
Peak exercise oxygen consumption (VO2) pre and post intervention
7 secondary outcomes
Skeletal Muscle Mass
Time frame: 20 weeks
Thigh Skeletal Muscle Mass
Time frame: 20 weeks
Thigh Muscle Composition
Time frame: 20 weeks
Muscle Strength
Time frame: 20 weeks
Muscle Quality
Time frame: 20 weeks
Quality of Life Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Time frame: 20 weeks
Quality of Life Measured by Short Form 36 Item Questionnaire (SF-36)
Time frame: 20 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38037817Schaich CL, Hughes TM, Kitzman DW, Jung Y, Chen H, Nicklas BJ, Houston DK, Brubaker PH, Molina AJA, Hugenschmidt CE. Neurocognitive Impairments and Their Improvement Following Exercise and Dietary Interventions in Older Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2024 Jan;17(1):e011134. doi: 10.1161/CIRCHEARTFAILURE.123.011134. Epub 2023 Dec 1. No abstract available.
- Derived from this study: PubMed 36314122Brubaker 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dalane W Kitzman, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing dietary, aerobic and resistance training and dietary, and aerobic exercise in people with Heart Failure, Diastolic and Obesity, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Exercise Oxygen Consumption (VO2) (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02636439, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2022.