Heart Failure With Preserved Ejection FractionNCT04506606
Cardiac Rehab Effects in HFpEF
A study testing Afferent block in people with Heart Failure With Preserved Ejection Fraction, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This research in Veterans with heart failure with preserved ejection fraction (HFpEF) will provide new information on the mechanisms determining the patients' exercise intolerance and the efficacy of regular physical activity to improve this shortcoming by alleviating the patients' neurocirculatory abnormalities. Read more about this study
- Who is it for?
- Ages 21 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Afferent block
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 2 May 2022to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- heart failure with preserved ejection fraction
Who cannot join
- heart failure with reduced ejection fraction
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001
About this study
Official title: Efficacy of Exercise Training in Patients With HFpEF
This research in Veterans with heart failure with preserved ejection fraction (HFpEF) will provide new information on the mechanisms determining the patients' exercise intolerance and the efficacy of regular physical activity to improve this shortcoming by alleviating the patients' neurocirculatory abnormalities. Specifically, the investigators will focus on the role of nerves originating in working limb muscles in determining the patients' exercise intolerance and compromised fatigue resistance before and after a chronic exercise intervention. By focusing on a specific mechanism, this project will evaluate the validity of exercise as an alternative treatment strategy with the overall purpose of improving the quality of life of Veterans with HFpEF.
Read the detailed description
Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by exercise intolerance and premature fatigue during physical activity. An abnormal exercise pressor reflex mediated by neural feedback from mechano- and/or metabosensitive group III and IV muscle afferents may contribute to these debilitating symptoms. However, little is known about the role and relative contribution of group III/IV afferents in circulatory control and fatigue development in patients with HFpEF. By studying both patients with HFpEF and well-matched controls, the investigators will evaluate the contribution of these muscle afferents to circulatory control and fatigue development, factors recognized to be major contributors to exercise intolerance. The investigators will use lumbar intrathecal fentanyl to block the central projection of group III/IV muscle afferents during voluntary and passive exercise (no concomitant effect on feedforward drive). This proven approach will enable us to evaluate, and distinguish between, the effects of group III and IV muscle afferents on central and peripheral hemodynamics during exercise, the exercise-induced development of central and peripheral fatigue (femoral nerve stimulation techniques), and on exercise tolerance. The investigators will also study muscle morphometry, baroreflex and chemoreflex sensitivity, and investigate intramuscular metabolic changes of the quadriceps during exercise using 31phosphorus magnetic resonance spectroscopy to evaluate disease-related alterations in cardiovascular reflex sensitivity and intrinsic muscle characteristics as a potential factor determining alterations in circulatory control and fatigue resistance in patients with HFpEF. Finally, the investigators will repeat these studies after a supervised 12-week knee-extension exercise training program, allowing us to investigate the effect of chronic exercise on the role of group III/IV muscle afferents in the hemodynamic response to exercise, the development of fatigue, and, ultimately, exercise tolerance. If this project confirms a significant contribution of group III/IV muscle afferents to the exercise intolerance exhibited by patients with HFpEF, and that chronic exercise can alleviate these impairments, the proposed work will provide the scientific basis for a paradigm shift in the treatment of this growing population.
- Being tested
- Afferent block
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Afferent blockProcedure or surgery
Block sensory feedback to evaluate hemodynamic and fatigue consequence of group III/IV muscle afferents
| Study group | Role | What they receive |
|---|---|---|
| Afferent effect on hemodynamics | Experimental | Evaluate impact of group III/IV muscle afferents on femoral blood flow Receives: Procedure: Afferent block |
| Afferent effect on fatigue | Experimental | Evaluate impact of group III/IV muscle afferents on exercise-induced changes in quadriceps twitch force Receives: Procedure: Afferent block |
| Effect of cardiac rehab | Experimental | Evaluate effect of chronic exercise on influence of muscle afferents on limb blood flow Receives: Procedure: Afferent block |
What is being measured
The primary outcome is the main question the study is designed to answer.
femoral blood flow
Quantifying femoral blood flow during exercise with and without afferent blockade
Measured: 1 hour
Secondary outcomes (1)
femoral blood flow
Impact of cardiac rehab on the influence of afferent blockade on femoral blood flow
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2020
- Study start2 May 2022
- Primary completion30 Sep 2026
- Study completion30 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Markus Amann, PhD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04506606
- Sponsor's protocol ID
- E3343-R
- Other IDs
- 5I01RX003343-05
- Status last verified
- Sep 2026
- First submitted
- 6 Aug 2020
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Exercise Training in Patients With HFpEF
- ClinicalTrials.gov ID
- NCT04506606
- Acronym / sponsor ID
- E3343-R
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 2 May 2022 (actual)
- Primary completion
- 30 Sep 2026 (actual)
- Study completion
- 30 Sep 2026 (actual)
- First posted
- 10 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research in Veterans with heart failure with preserved ejection fraction (HFpEF) will provide new information on the mechanisms determining the patients' exercise intolerance and the efficacy of regular physical activity to improve this shortcoming by alleviating the patients' neurocirculatory abnormalities. Specifically, the investigators will focus on the role of nerves originating in working limb muscles in determining the patients' exercise intolerance and compromised fatigue resistance before and after a chronic exercise intervention. By focusing on a specific mechanism, this project will evaluate the validity of exercise as an alternative treatment strategy with the overall purpose of improving the quality of life of Veterans with HFpEF.
Detailed description
Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by exercise intolerance and premature fatigue during physical activity. An abnormal exercise pressor reflex mediated by neural feedback from mechano- and/or metabosensitive group III and IV muscle afferents may contribute to these debilitating symptoms. However, little is known about the role and relative contribution of group III/IV afferents in circulatory control and fatigue development in patients with HFpEF. By studying both patients with HFpEF and well-matched controls, the investigators will evaluate the contribution of these muscle afferents to circulatory control and fatigue development, factors recognized to be major contributors to exercise intolerance. The investigators will use lumbar intrathecal fentanyl to block the central projection of group III/IV muscle afferents during voluntary and passive exercise (no concomitant effect on feedforward drive). This proven approach will enable us to evaluate, and distinguish between, the effects of group III and IV muscle afferents on central and peripheral hemodynamics during exercise, the exercise-induced development of central and peripheral fatigue (femoral nerve stimulation techniques), and on exercise tolerance. The investigators will also study muscle morphometry, baroreflex and chemoreflex sensitivity, and investigate intramuscular metabolic changes of the quadriceps during exercise using 31phosphorus magnetic resonance spectroscopy to evaluate disease-related alterations in cardiovascular reflex sensitivity and intrinsic muscle characteristics as a potential factor determining alterations in circulatory control and fatigue resistance in patients with HFpEF. Finally, the investigators will repeat these studies after a supervised 12-week knee-extension exercise training program, allowing us to investigate the effect of chronic exercise on the role of group III/IV muscle afferents in the hemodynamic response to exercise, the development of fatigue, and, ultimately, exercise tolerance. If this project confirms a significant contribution of group III/IV muscle afferents to the exercise intolerance exhibited by patients with HFpEF, and that chronic exercise can alleviate these impairments, the proposed work will provide the scientific basis for a paradigm shift in the treatment of this growing population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Afferent effect on hemodynamics | Experimental | Procedure: Afferent blockEvaluate impact of group III/IV muscle afferents on femoral blood flow |
| Afferent effect on fatigue | Experimental | Procedure: Afferent blockEvaluate impact of group III/IV muscle afferents on exercise-induced changes in quadriceps twitch force |
| Effect of cardiac rehab | Experimental | Procedure: Afferent blockEvaluate effect of chronic exercise on influence of muscle afferents on limb blood flow |
Who may qualify
- Ages
- 21 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- heart failure with preserved ejection fraction
Key exclusion criteria (1 listed)
- heart failure with reduced ejection fraction
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 |
|---|---|---|
| Afferent blockBlock sensory feedback to evaluate hemodynamic and fatigue consequence of group III/IV muscle afferents | Procedure or surgery | Afferent effect on fatigue, Afferent effect on hemodynamics, Effect of cardiac rehab |
Primary outcome
femoral blood flow
Time frame: 1 hour
Quantifying femoral blood flow during exercise with and without afferent blockade
1 secondary outcome
femoral blood flow
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- 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.
Markus Amann, PhD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Afferent block in people with Heart Failure With Preserved Ejection Fraction, run by VA Office of Research and Development 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 1 inclusion and 1 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 6 Oct 2026. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
femoral blood flow (time frame: 1 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Oct 2026.