Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT04506606 |
Other study ID # |
E3343-R |
Secondary ID |
|
Status |
Recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
May 2, 2022 |
Est. completion date |
September 30, 2026 |
Study information
Verified date |
June 2023 |
Source |
VA Office of Research and Development |
Contact |
Misti R Seppi, MBA BS AAS |
Phone |
(801) 582-1565 |
Email |
Misti.Seppi[@]va.gov |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical 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. 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.
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.