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Heart FailureEarly Phase 1NCT02209610

Premature Fatigue in Veterans With Heart Failure: Neuronal Influences

A Early Phase 1 study testing Electrical and Magnetic Nerve Stimulators and Intrathecal Fentanyl in people with Heart Failure, run by VA Office of Research and Development at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

A hallmark of patients with heart failure (HF) is premature fatigue which impairs their quality of life and depicts a major source of morbidity. Premature fatigue may be attributed to a) contraction-induced transient changes within muscles (i.e. Read more about this study

Who is it for?
Ages 20 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Heart Failure
What is being tested?
Electrical and Magnetic Nerve Stimulators and Intrathecal Fentanyl
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
1 Jul 2015to 15 Jan 2017
Phase
Early Phase 1
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 20 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, >1yr duration, ages 20-75 yr),
  • not pacemaker dependent (no biventricular pacers),
  • NYHA class II and III symptoms,
  • Left ventricular ejection fraction (LVEF)<35%,
  • no or minimal smoking history (<15 pk yrs) and on stable medications.
  • The investigators will also study subjects with preserved ejection fraction
Show all 13Show fewer
  • heart failure with a preserved ejection fraction (HFpEF);
  • LVEF >50%,
  • >1yr duration,
  • ages 20-75 yr,
  • not pacemaker dependent,
  • NYHA class II and III symptoms,
  • no or minimal smoking history (<15 pk yrs) and on stable medications. The investigators will exclude morbidly obese patients (BMI >35), patients with uncontrolled hypertension (>160/100), anemia (Hgb<9) and severe renal insufficiency (individuals with creatinine clearance <30 by the Cockcroft-Gault formula).

Who cannot join

  • Patients with significant non-cardiac comorbidities, which if present could alter the study results, will be excluded.
  • Patients will be sedentary, defined here as no regular physical activity for at least the prior 6 months and current activity level will be documented by an activity questionnaire.
  • Candidates must have no orthopedic limitations that would prohibit them from performing exercise.
  • Due to the typical age of patients with heart failure, all women will be postmenopausal (either natural or surgical) defined as a cessation of menses for at least 2 years,
  • and in women without a uterus, follicle stimulating hormone (FSH) >40 IU/L.
  • Women currently taking hormone replacement therapy (HRT) will be excluded from the proposed studies due to the direct vascular effects of HRT.
  • Patients with a pacemaker and / or defibrillator will be excluded from the study due to the use of a magnetic/electric stimulators.

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

Other trials in United States

About this study

A hallmark of patients with heart failure (HF) is premature fatigue which impairs their quality of life and depicts a major source of morbidity. Premature fatigue may be attributed to a) contraction-induced transient changes within muscles (i.e. peripheral fatigue) and/or b) failure of the central nervous system to 'drive' / activate locomotor muscles (i.e. central fatigue). Both determinants of fatigue can lead to a reduction in a muscle's force and power generating capacity and to a compromised ability to perform whole body activities (e.g. walking). Recent findings in health have documented that group III/IV afferent fibers from the working muscle play a critical role in the development of both components of fatigue. Specifically, group III/IV muscle afferents limit central motor drive (CMD) during exercise and thereby exaggerate the development of central fatigue. In contrast, muscle afferents optimize muscle O2 delivery through the precise regulation of circulation and ventilation during exercise and thereby attenuate the development of peripheral fatigue.

Read the detailed description

Recent findings in HF suggest an altered effect of group III/IV muscle afferents in this population. Although normal afferent feedback is crucial for adequate O2 delivery during exercise, excessive neural feedback has substantial negative consequences. HF patients are characterized by augmented neural feedback arising from overactive muscle afferents. It has been hypothesized that this abnormality compromises locomotor muscle O2 delivery in these patients. Therefore, the abnormally elevated muscle afferent feedback in HF might exacerbate, compared to healthy age- and activity matched individuals (CTRLs), the development of both peripheral (via limiting O2 delivery) and central (via restricting CMD) fatigue during exercise. Recent advances in non-invasive stimulation techniques offer a genuine opportunity to identify the sites and synaptic mechanisms that mediate central and peripheral fatigue including alterations in the responsiveness of the corticospinal tract (i.e. a determinant of central fatigue). Taken together, the proposed studies aim to determine the impact of HF on the precise development of central and peripheral fatigue during both whole body and single muscle exercise and evaluate the extent to which group III/IV muscle afferents contribute to this development.

Conditions
Heart Failure
Being tested
Electrical and Magnetic Nerve Stimulators, Intrathecal Fentanyl
Keywords
Heart Failure
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Electrical and Magnetic Nerve StimulatorsDevice

    Stimulation of motor nerve and central nervous system

  • Intrathecal FentanylDrug

    Mu-opioid receptor agonist

Study groups in NCT02209610
Study groupRoleWhat they receive
Patients With Heart Failure: Neuromuscular AbnormalitiesOtherPatients with Heart Failure
Receives: Device: Electrical and Magnetic Nerve Stimulators; Drug: Intrathecal Fentanyl
Health Control Subjects and Neuromuscular FunctionOtherHealth Control Subjects
Receives: Device: Electrical and Magnetic Nerve Stimulators; Drug: Intrathecal Fentanyl

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximal Voluntary Quadriceps Force [% Change From Baseline]

    Following dynamic single leg knee extension exercise for a given duration (4-8 min), the decline in maximal voluntary contraction force will be measured.

    Measured: 1 minute after exercise on study day

  2. Quadriceps Twitch Force and Voluntary Activation (% Change From Baseline)

    During a 2-min maximal voluntary quadriceps contraction, central and peripheral fatigue will develop progressively and significantly more in HF vs. CTRLs.

    Measured: During (20 second intervals) and 1 minute after exercise on study day

  3. Muscle Afferent Affect

    Corticospinal responsiveness will be quantified before and after exercise.

    Measured: 1 minute after exercise on study day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2014 (estimated)
  2. Study start1 Jul 2015
  3. Primary completion15 Jan 2017
  4. Study completion15 Jan 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02209610
Sponsor's protocol ID
E1572-P
Status last verified
Jun 2019
First submitted
10 Jul 2014
Last updated
2 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ives SJ, Amann M, Venturelli M, Witman MA, Groot HJ, Wray DW, Morgan DE, Stehlik J, Richardson RS. The Mechanoreflex and Hemodynamic Response to Passive Leg Movement in Heart Failure. Med Sci Sports Exerc. 2016 Mar;48(3):368-76. doi: 10.1249/MSS.0000000000000782.

    PubMed 26418560

  • Sidhu SK, Weavil JC, Venturelli M, Rossman MJ, Gmelch BS, Bledsoe AD, Richardson RS, Amann M. Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans. Am J Physiol Heart Circ Physiol. 2015 Nov;309(9):H1479-89. doi: 10.1152/ajpheart.00433.2015. Epub 2015 Sep 18.

    PubMed 26386110

  • Weavil JC, Sidhu SK, Mangum TS, Richardson RS, Amann M. Fatigue diminishes motoneuronal excitability during cycling exercise. J Neurophysiol. 2016 Oct 1;116(4):1743-1751. doi: 10.1152/jn.00300.2016. Epub 2016 Jul 20.

    PubMed 27440242

  • Amann M, Sidhu SK, Weavil JC, Mangum TS, Venturelli M. Autonomic responses to exercise: group III/IV muscle afferents and fatigue. Auton Neurosci. 2015 Mar;188:19-23. doi: 10.1016/j.autneu.2014.10.018. Epub 2014 Oct 23.

    PubMed 25458423

  • Wray DW, Amann M, Richardson RS. Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction. Heart Fail Rev. 2017 Mar;22(2):149-166. doi: 10.1007/s10741-016-9573-4.

    PubMed 27392715

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Electrical and Magnetic Nerve Stimulators and Intrathecal Fentanyl in people with Heart Failure, 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 13 inclusion and 7 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 2 Aug 2019. 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.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Aug 2019). 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?

Maximal Voluntary Quadriceps Force [% Change From Baseline] (time frame: 1 minute after exercise on study day). The study lists 3 primary outcomes in all. 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 NCT02209610, which also lists 5 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 2 Aug 2019.

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