FatigueNCT01059994
Role of Skeletal Muscle Nitric Oxide Production in Age-related Fatigue and Fatigability
A study testing Sildenafil in people with Fatigue and Aging, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
Trial summary
This is a pilot study funded by the National Institutes of Health. In this project, we will investigate the potential effect of skeletal muscle nitric oxide (NO) production on muscle strength and physical function in older individuals. Read more about this study
- Who is it for?
- Ages 20 to 80 years, men onlyHealthy volunteers can take part
- What is being tested?
- Sildenafil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jul 2013
- 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 20 to 80 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1. Age 20-35 yrs, and 60-80 yrs.
- 2. Ability to sign consent form (score >23 on the 30-item Mini Mental State Examination, MMSE)
- 3. Stable body weight for at least 3 months
Who cannot join
- 1. Physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (>2/year) or significant weight loss in the past year)
- 2. Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
- 3. Pregnancy
- 4. Significant heart, liver, kidney, blood or respiratory disease
- 5. Peripheral vascular disease
- 6. Diabetes mellitus or other untreated endocrine disease
Show all 13Show fewer
- 7. Active cancer
- 8. Use of nitrates
- 9. Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
- 10. Alcohol or drug abuse
- 11. Severe depression (>5 on the 15-item Geriatric Depression Scale, GDS)
- 12. Cardiac abnormalities such as a cardiac shunt or previously diagnosed pulmonary hypertension.
- 13. Systolic blood pressure <100 or >150, diastolic blood pressure <60 or >90.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Medical Branch
Galveston, Texas, 77555
About this study
This is a pilot study funded by the National Institutes of Health. In this project, we will investigate the potential effect of skeletal muscle nitric oxide (NO) production on muscle strength and physical function in older individuals. We propose to test a new method that may enable simultaneous determination of both vascular and skeletal muscle NO production for the first time in humans. Further, we will determine whether augmentation of NO-mediated responses, by administration of sildenafil citrate (Viagra), reduces fatigue and fatigability in older individuals.
Read the detailed description
Fatigue is highly prevalent and associated with future mortality in older individuals. Even in non-disabled older persons, fatigue may be the primary reason for activity limitation. However, understanding the etiology of fatigue in this population has been hampered by differing or imprecise definitions of fatigue. As a result, the term fatigue has been proposed to refer to the subjective experience of tiredness or lack of energy, whereas the term fatigability should refer to the susceptibility to fatigue induced by activity of any kind (mental, physical, etc). Skeletal muscle activity can contribute to the perception of overall fatigue as well as produce a type of localized fatigue within skeletal muscle. Skeletal muscle fatigue is defined as a decline in skeletal muscle performance resulting from muscle activity.
We hypothesize that skeletal muscle NO-mediated responses are reduced with aging due to decreased skeletal muscle NO production. NO is well-known to elicit vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle perfusion may influence both skeletal muscle and overall fatigue. To measure skeletal muscle NO production, we will infuse a stable isotope tracer of arginine, the precursor of NO, and measure its conversion across the leg and in skeletal muscle to citrulline (which is another product of the reaction that produces NO). If successful, this method will allow the study of relative changes in vascular and muscle NO production that occur with aging and other conditions (e.g., hypertension, Duchenne muscular dystrophy). We will also determine whether age-related differences in muscle perfusion and NO-cGMP signaling exist between younger and older groups. As impaired redox homeostasis and ryanodine receptor S-nitrosylation and phosphorylation have been implicated in skeletal muscle fatigue, we will assess skeletal muscle redox homeostasis and ryanodine receptor S-nitrosylation in these experiments. We hypothesize that aging will shift muscle redox homeostasis to a more oxidized state.
- Being tested
- Placebo sildenafil, Sildenafil
- Keywords
- fatigue, aging
- Medical subject headings
- Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo sildenafilDrug
Also called Viagra
Oral, daily, 1 week.
SildenafilDrug
Also called Viagra
oral, 25mg, daily for 1 week
| Study group | Role | What they receive |
|---|---|---|
| placebo sildenafil young | Placebo comparator | Younger subjects (ages 20-35) were administered placebo sildenafil orally daily for 1 week. Receives: Drug: Placebo sildenafil |
| sildenafil young | Experimental | Younger subjects (ages 20 -35) were administered sildenafil daily (25 mg/day) orally for 1 week. Receives: Drug: Sildenafil |
| placebo sildenafil older | Placebo comparator | Older subjects (ages 60-80) were administered placebo sildenafil orally daily for 1 week. Receives: Drug: Placebo sildenafil |
| sildenafil older | Experimental | Older subjects (ages 60 - 80) were administered sildenafil daily (25 mg/day) orally for 1 week. Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Muscle Fatigue After 1 Week of Placebo or Sildenafil
Muscle fatigue was tested before and after 1 week of placebo/sildenafil (25mg/day) treatment.
Subjects were asked to perform maximum effort isokinetic knee extensions until force production reached 50% of their MVC (maximum voluntary contraction). Data was collected as number of successful repetitions completed between start and 50% MVC.
Data is presented as percent change in repetitions (1 week of treatment / baseline).
Measured: baseline to 1 week
Secondary outcomes (1)
Protein Synthesis Rate After 1 Week of Sildenafil or Placebo
Skeletal muscle protein synthesis, measured as the fractional synthesis rate (the percent of the total synthesized per unit time) after 1 week of either Placebo or Sildenafil (25 mg/day). Example: if FSR = 0.06 hr-1 it means that 6% of proteins in a given sample were synthesized in the last hour or proteins is synthesized at 6% per hour. A higher rate means that more synthesis is occurring.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2010 (estimated)
- Study startJan 2010
- Primary completionJul 2013
- Study completionJul 2013
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.
- Other trials for FatigueStudies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- William Durham, Ph.D., Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01059994
- Sponsor's protocol ID
- 09-213
- Status last verified
- Nov 2018
- First submitted
- 28 Jan 2010
- Last updated
- 11 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Skeletal Muscle Nitric Oxide Production in Age-related Fatigue and Fatigability
- ClinicalTrials.gov ID
- NCT01059994
- Acronym / sponsor ID
- 09-213
- Keywords
- fatigue, aging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Study start
- Jan 2010
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 1 Feb 2010 (estimated)
- Results
- Posted 23 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study funded by the National Institutes of Health. In this project, we will investigate the potential effect of skeletal muscle nitric oxide (NO) production on muscle strength and physical function in older individuals. We propose to test a new method that may enable simultaneous determination of both vascular and skeletal muscle NO production for the first time in humans. Further, we will determine whether augmentation of NO-mediated responses, by administration of sildenafil citrate (Viagra), reduces fatigue and fatigability in older individuals.
Detailed description
Fatigue is highly prevalent and associated with future mortality in older individuals. Even in non-disabled older persons, fatigue may be the primary reason for activity limitation. However, understanding the etiology of fatigue in this population has been hampered by differing or imprecise definitions of fatigue. As a result, the term fatigue has been proposed to refer to the subjective experience of tiredness or lack of energy, whereas the term fatigability should refer to the susceptibility to fatigue induced by activity of any kind (mental, physical, etc). Skeletal muscle activity can contribute to the perception of overall fatigue as well as produce a type of localized fatigue within skeletal muscle. Skeletal muscle fatigue is defined as a decline in skeletal muscle performance resulting from muscle activity.
We hypothesize that skeletal muscle NO-mediated responses are reduced with aging due to decreased skeletal muscle NO production. NO is well-known to elicit vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle perfusion may influence both skeletal muscle and overall fatigue. To measure skeletal muscle NO production, we will infuse a stable isotope tracer of arginine, the precursor of NO, and measure its conversion across the leg and in skeletal muscle to citrulline (which is another product of the reaction that produces NO). If successful, this method will allow the study of relative changes in vascular and muscle NO production that occur with aging and other conditions (e.g., hypertension, Duchenne muscular dystrophy). We will also determine whether age-related differences in muscle perfusion and NO-cGMP signaling exist between younger and older groups. As impaired redox homeostasis and ryanodine receptor S-nitrosylation and phosphorylation have been implicated in skeletal muscle fatigue, we will assess skeletal muscle redox homeostasis and ryanodine receptor S-nitrosylation in these experiments. We hypothesize that aging will shift muscle redox homeostasis to a more oxidized state.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| placebo sildenafil young | Placebo comparator | Drug: Placebo sildenafilYounger subjects (ages 20-35) were administered placebo sildenafil orally daily for 1 week. |
| sildenafil young | Experimental | Drug: SildenafilYounger subjects (ages 20 -35) were administered sildenafil daily (25 mg/day) orally for 1 week. |
| placebo sildenafil older | Placebo comparator | Drug: Placebo sildenafilOlder subjects (ages 60-80) were administered placebo sildenafil orally daily for 1 week. |
| sildenafil older | Experimental | Drug: SildenafilOlder subjects (ages 60 - 80) were administered sildenafil daily (25 mg/day) orally for 1 week. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 1. Age 20-35 yrs, and 60-80 yrs.
- 2. Ability to sign consent form (score >23 on the 30-item Mini Mental State Examination, MMSE)
- 3. Stable body weight for at least 3 months
Key exclusion criteria (13 listed)
- 1. Physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (>2/year) or significant weight loss in the past year)
- 2. Exercise training (>2 weekly sessions of moderate to high intensity aerobic or resistance exercise)
- 3. Pregnancy
- 4. Significant heart, liver, kidney, blood or respiratory disease
- 5. Peripheral vascular disease
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 |
|---|---|---|
| Placebo sildenafilAlso: ViagraOral, daily, 1 week. | Drug | placebo sildenafil older, placebo sildenafil young |
| SildenafilAlso: Viagraoral, 25mg, daily for 1 week | Drug | sildenafil older, sildenafil young |
Primary outcome
Change in Muscle Fatigue After 1 Week of Placebo or Sildenafil
Time frame: baseline to 1 week
Muscle fatigue was tested before and after 1 week of placebo/sildenafil (25mg/day) treatment. Subjects were asked to perform maximum effort isokinetic knee extensions until force production reached 50% of their MVC (maximum voluntary contraction). Data was collected as number of successful repetitions completed between start and 50% MVC. Data is presented as percent change in repetitions (1 week of treatment / baseline).
1 secondary outcome
Protein Synthesis Rate After 1 Week of Sildenafil or Placebo
Time frame: 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
William Durham, Ph.D. principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sildenafil in people with Fatigue and Aging, run by The University of Texas Medical Branch, Galveston 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 3 inclusion and 13 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 11 Feb 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. Some participants in this study may receive a placebo. 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 23 Dec 2015). 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?
Change in Muscle Fatigue After 1 Week of Placebo or Sildenafil (time frame: baseline to 1 week). 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 11 Feb 2019.