Chronic Heart FailurePhase 1NCT01919918
Muscle Afferent Feedback Effects in Patients With Heart Failure
A Phase 1 study testing Muscle Contraction with Metabolite Solution Administration in people with Chronic Heart Failure, run by University of Utah at 2 sites in United States.
Trial summary
The purpose of the study is to find out more about the mechanism by which neural feedback from the working muscle affects the development of central fatigue during exercise. Subjects with chronic heart failure (HF) and healthy subject counterparts will be tested to determine the mechanisms accounting for the premature… Read more about this study
- Who is it for?
- Ages 20 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Heart Failure
- What is being tested?
- Muscle Contraction with Metabolite Solution Administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2013to 3 Jan 2018
- Phase
- Phase 1
- 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 20 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Heart Failure Inclusion Criteria:
- Subjects with a history of stable cardiomyopathy (ischemic and non-ischemic, greater than 1 year duration, ages 20-79 years)
- New York Heart Association class I through IV symptoms
- Left ventricular ejection fraction less than 35 percent (heart failure patients with reduced left ventricular ejection fraction) or greater than 50 percent (heart failure patients with preserved left ventricular ejection fraction)
- Sedentary, no regular physical activity for at least 6 months prior
- Post-menopausal for at least 2 years and follicle stimulating hormone greater than 40
Heart Failure Exclusion Criteria:
- Patients with atrial fibrillation or heart failure believed to be secondary to atrial fibrillation
- Morbidly obese patients with a body mass index greater than 35
- Patients with uncontrolled hypertension, greater than 160/100
- Anemia with a hemoglobin less than 9
- Severe renal insufficiency (creatinine clearance less than 30 by the Cockcroft-Gault formula)
- Patients with significant non-cardiac comorbidities
- Orthopedic limitations that would prohibit them from performing the elbow-flexor exercise
- Current smoker or smoking history of 15 packs or more per year
- Women currently taking hormone replacement therapy
Healthy Control Inclusion Criteria:
- Ages 20-75 years
- Sedentary, no regular physical activity for at least 6 months prior
- Post-menopausal for at least 2 years and follicle stimulating hormone greater than 40
Healthy Control Exclusion Criteria:
- History of cardiovascular related abnormalities or pulmonary abnormalities
- Morbidly obese patients with a body mass index greater than 35
- Patients with uncontrolled hypertension, greater than 160/100
- Anemia with a hemoglobin less than 9
- Orthopedic limitations that would prohibit them from performing the elbow-flexor exercise
- Current smoker or smoking history of 15 packs or more per year
- Women currently taking hormone replacement therapy
Trial locations and contacts
2 sites in 1 country.
United States2 sites
George E Wahlen Vetern Affairs Medical Center
Salt Lake City, Utah, 84148
Veterans Affairs Salt Lake City Heath Care System
Salt Lake City, Utah, 84148
About this study
Official title: Muscle Afferent Feedback Effects in Patients With Heart Failure: The Development of Central Fatigue
The purpose of the study is to find out more about the mechanism by which neural feedback from the working muscle affects the development of central fatigue during exercise. Subjects with chronic heart failure (HF) and healthy subject counterparts will be tested to determine the mechanisms accounting for the premature fatigue characterizing HF patients during physical activity.
Read the detailed description
A substantial part in limiting exercise and/or physical activity in humans results from the development of peripheral and central fatigue during physical activity. Peripheral fatigue comprises biochemical changes within the metabolic milieu of the working muscle leading to an attenuated response to neural excitation, while central fatigue comprises a failure of the central nervous system to drive motoneurons.
Patients with HF have overactive group III/IV muscle afferents and an exaggerated development of central fatigue during physical activity that is not explained by their reduced physical conditioning or cardiac insufficiency caused by their failing heart. The exact mechanisms accounting for the exaggerated central fatigue in HF remains elusive, however, the development of central fatigue during exercise has recently been linked to signaling by group III/IV muscle afferents. This makes the heightened neural feedback in HF a likely candidate for these patients' increased susceptibility to central fatigue.
Lower pH, increased lactate and increased adenosine triphosphate has been shown to activate group III/IV afferents in a physiological manner and thus induce, in a rested and unfatigued muscle, the intramuscular milieu associated with moderate to heavy exercise. The objective of this study is to quantitate and compare the sensitivity of group III/IV afferents and associated effects on central fatigue in HF patients and healthy controls when skeletal muscle is subject to controlled lower pH, increased lactate and increased adenosine triphosphate.
- Conditions
- Chronic Heart Failure
- Being tested
- Muscle Contraction with Metabolite Solution Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Muscle Contraction with Metabolite Solution AdministrationDrug
Also called adenosine triphosphate, lactate, and protons with phosphate buffer
Participants will perform maximal elbow flexor or knee extensor contractions before and after administration of metabolite solutions of pH 7.2, pH 7.0 and pH 6.6
| Study group | Role | What they receive |
|---|---|---|
| Heart Failure Patients | Other | Patients with heart failure will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer. Receives: Drug: Muscle Contraction with Metabolite Solution Administration |
| Control Participants | Other | Healthy control participants will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer. Receives: Drug: Muscle Contraction with Metabolite Solution Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Elbow Flexor Maximal Voluntary Contraction in newton-meters
Measured: 2 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2013 (estimated)
- Study startSep 2013
- Primary completion3 Jan 2018
- Study completion3 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Heart FailureStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Markus Amann, University of Utah
- Investigators
- Markus Amann, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01919918
- Sponsor's protocol ID
- 62914
- Status last verified
- Jan 2018
- First submitted
- 29 Jul 2013
- Last updated
- 8 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Muscle Afferent Feedback Effects in Patients With Heart Failure: The Development of Central Fatigue
- ClinicalTrials.gov ID
- NCT01919918
- Acronym / sponsor ID
- 62914
- Conditions
- Chronic Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- 3 Jan 2018 (actual)
- Study completion
- 3 Jan 2018 (actual)
- First posted
- 9 Aug 2013 (estimated)
- 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.
The purpose of the study is to find out more about the mechanism by which neural feedback from the working muscle affects the development of central fatigue during exercise. Subjects with chronic heart failure (HF) and healthy subject counterparts will be tested to determine the mechanisms accounting for the premature fatigue characterizing HF patients during physical activity.
Detailed description
A substantial part in limiting exercise and/or physical activity in humans results from the development of peripheral and central fatigue during physical activity. Peripheral fatigue comprises biochemical changes within the metabolic milieu of the working muscle leading to an attenuated response to neural excitation, while central fatigue comprises a failure of the central nervous system to drive motoneurons.
Patients with HF have overactive group III/IV muscle afferents and an exaggerated development of central fatigue during physical activity that is not explained by their reduced physical conditioning or cardiac insufficiency caused by their failing heart. The exact mechanisms accounting for the exaggerated central fatigue in HF remains elusive, however, the development of central fatigue during exercise has recently been linked to signaling by group III/IV muscle afferents. This makes the heightened neural feedback in HF a likely candidate for these patients' increased susceptibility to central fatigue.
Lower pH, increased lactate and increased adenosine triphosphate has been shown to activate group III/IV afferents in a physiological manner and thus induce, in a rested and unfatigued muscle, the intramuscular milieu associated with moderate to heavy exercise. The objective of this study is to quantitate and compare the sensitivity of group III/IV afferents and associated effects on central fatigue in HF patients and healthy controls when skeletal muscle is subject to controlled lower pH, increased lactate and increased adenosine triphosphate.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Heart Failure Patients | Other | Drug: Muscle Contraction with Metabolite Solution AdministrationPatients with heart failure will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer. |
| Control Participants | Other | Drug: Muscle Contraction with Metabolite Solution AdministrationHealthy control participants will undergo intervention of muscle contraction with metabolite solution administration. Maximal voluntary muscle contraction exercise with varying metabolite solution administration of adenosine triphosphate, lactate, and protons with phosphate buffer. |
Who may qualify
- Ages
- 20 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Muscle Contraction with Metabolite Solution AdministrationAlso: adenosine triphosphate, lactate, and protons with phosphate bufferParticipants will perform maximal elbow flexor or knee extensor contractions before and after administration of metabolite solutions of pH 7.2, pH 7.0 and pH 6.6 | Drug | Control Participants, Heart Failure Patients |
Primary outcome
Elbow Flexor Maximal Voluntary Contraction in newton-meters
Time frame: 2 minutes
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 8 Jan 2018.
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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
University of Utah
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Muscle Contraction with Metabolite Solution Administration in people with Chronic Heart Failure, run by University of Utah at 2 sites 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?
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 8 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Elbow Flexor Maximal Voluntary Contraction in newton-meters (time frame: 2 minutes). 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 8 Jan 2018.