- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01059994
Role of Skeletal Muscle Nitric Oxide Production in Age-related Fatigue and Fatigability
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Texas
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Galveston, Texas, United States, 77555
- University of Texas Medical Branch
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo sildenafil young
Younger subjects (ages 20-35) were administered placebo sildenafil orally daily for 1 week.
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Oral, daily, 1 week.
Other Names:
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Experimental: sildenafil young
Younger subjects (ages 20 -35) were administered sildenafil daily (25 mg/day) orally for 1 week.
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oral, 25mg, daily for 1 week
Other Names:
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Placebo Comparator: placebo sildenafil older
Older subjects (ages 60-80) were administered placebo sildenafil orally daily for 1 week.
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Oral, daily, 1 week.
Other Names:
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Experimental: sildenafil older
Older subjects (ages 60 - 80) were administered sildenafil daily (25 mg/day) orally for 1 week.
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oral, 25mg, daily for 1 week
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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). |
baseline to 1 week
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Protein Synthesis Rate After 1 Week of Sildenafil or Placebo
Time Frame: 1 week
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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.
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1 week
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Collaborators and Investigators
Investigators
- Principal Investigator: William Durham, Ph.D., University of Texas
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09-213
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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