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The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue

This study is currently recruiting participants.
Verified May 2013 by The University of Texas, Galveston
Sponsor:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT01661595
First received: August 7, 2012
Last updated: May 15, 2013
Last verified: May 2013
History of Changes
  Purpose

This study is funded by the Moody Endowment. In this project, we will investigate the potential effect of skeletal muscle nitric oxide (NO) production on skeletal muscle anabolism, muscle strength, physical function, and body composition in older individuals. Further, we will determine whether augmentation of NO-mediated signaling reduces fatigue and fatigability.


Condition Intervention
Fatigue
 Drug: Sildenafil
Drug: tadalafil
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue.

Resource links provided by NLM:

MedlinePlus related topics: Fatigue
U.S. FDA Resources

Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Perceptual Fatigue [ Time Frame: Acutely at 1 week and 4 weeks ] [ Designated as safety issue: No ]

    Determining if fatigue changes relative to baseline are different in treatment groups (Sildenafil, Tadalafil) at 1 week and 4 weeks as compared with placebo.

    Determining if fatigue changes at 1 week and 4 weeks are different between treatment groups (Sildenafil, Tadalafil).


  • Skeletal Muscle Fatigue [ Time Frame: Acutely at 1 week and 4 weeks ] [ Designated as safety issue: No ]

    Determining if fatigue changes relative to baseline are different in treatment groups (Sildenafil, Tadalafil) at 1 week and 4 weeks as compared with placebo.

    Determining if fatigue changes at 1 week and 4 weeks are different between treatment groups (Sildenafil, Tadalafil).



Secondary Outcome Measures:
  • Fractional Synthesis Rate [ Time Frame: Acutely at 1 day and 1 week ] [ Designated as safety issue: No ]

    Determining if skeletal muscle protein fractional synthesis rate changes relative to baseline are different in treatment groups (Sildenafil, Tadalafil) at 1 day and 1 week as compared with placebo.

    Determining if skeletal muscle protein synthesis rate changes relative to baseline are different between treatment groups (Sildenafil, Tadalafil) at 1 day and 1 week of treatment



Estimated Enrollment: 72
Study Start Date: November 2012
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sildenafil
50 mg/day Sildenafil Other Name: Viagra, Revatio
 Drug: Sildenafil
50 mg/day for 4 weeks
Other Names:
  • Viagra
  • Revatio
Drug: tadalafil
10 mg/day for 4 weeks.
Other Names:
  • Cialis
  • Adcirca
Active Comparator: tadalafil
10 mg/day Tadalafil Other Name: Cialis, Adcirca
 Drug: tadalafil
10 mg/day for 4 weeks.
Other Names:
  • Cialis
  • Adcirca
Placebo Comparator: Placebo
Placebo (crossed-over to 50 mg/day Sildenafil after 4 weeks) ; Placebo (crossed-over to 10 mg/day Tadalafil after 4 weeks)
 Drug: Placebo
Placebo 1 capsule per day for four weeks.

Detailed Description:

The Investigators hypothesize that upregulation of skeletal muscle NO-cGMP mediated responses through phosphodiesterase (PDE) inhibition by sildenafil or tadalafil causes an acute anabolic response of skeletal muscle protein synthesis. NO is well-known to elicit vasodilation through stimulation of cGMP signaling, and NO-mediated changes in muscle perfusion may influence both skeletal muscle anabolism and perceptual fatigue. To measure skeletal muscle protein synthesis, we will infuse a stable isotope tracer of phenylalanine and measure its incorporation into skeletal muscle proteins following a dose of sildenafil, tadalafil, or placebo. The Investigators will also determine whether differences exist between men and women in response to PDE inhibition. As skeletal muscle NO-cGMP signaling has been implicated in fatigue responses, we will assess the acute effect of sildenafil and tadalafil on fatigue. Fatigue can be manifested both as a performance deficit at a local level (e.g., a reduced ability of skeletal muscle to produce power or force) as well as a subjective experience of lacking physical or mental energy. Accordingly, we will use more than one means (skeletal muscle performance, fatigue questionnaires, accelerometers) to study fatigue. The Investigators hypothesize that sildenafil or tadalafil will acutely reduce exercise-associated fatigability and skeletal muscle fatigue development

  Eligibility

Ages Eligible for Study:   50 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 50-60 years of age
  2. Ability to sign consent form (score>23 on the 30-item Mini Mental Status examination, MMSE)
  3. Stable body weight for at least three 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. Pregnancy
  3. Significant heart, liver, kidney, blood or respiratory disease.
  4. Peripheral vascular disease.
  5. Diabetes mellitus or other untreated endocrine disease.
  6. Active cancer
  7. Use of nitrates.
  8. Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
  9. Alcohol or drug abuse.
  10. Severe depression (>5 on the 15-item Geriatric Depression Scale, GDS).
  11. Cardiac abnormalities such as cardiac shunt or previously diagnosed pulmonary hypertension.
  12. Systolic blood pressure <100 or>150, diastolic blood pressure <60 or 90>. This range is smaller than the acceptable range stated in the prescribing information for sildenafil/tadalafil (90/50 and <170/110).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01661595

Contacts
Contact: Kathleen M. Randolph, B.S. (409) 772-8126 kmrandol@utmb.edu
Contact: William J. Durham, PhD (409) 772-8702 wjdurham@utmb.edu

Locations
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555-0361
Contact: Clinical Trial Office - University of Texas Medical Branch     409-772-1950        
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: Melinda Sheffield-Moore, PhD University of Texas Medical Branch, Galveston
  More Information

No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT01661595     History of Changes
Other Study ID Numbers: 12-153
Study First Received: August 7, 2012
Last Updated: May 15, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas, Galveston:
Fatigue
Fatigability
Surface Electromyography (sEMG)
cyclic guanosine monophosphate (cGMP)
Nitric Oxide (NO)
NO-cGMP
Phosphodiesterase (PDE)
Sildenafil
 Tadalafil
Isotope
Infusion
Anabolism
Upregulation
Accelerometer
Placebo
Nitrosylation

Additional relevant MeSH terms:
Fatigue
Signs and Symptoms
Sildenafil
Tadalafil
Vasodilator Agents
Cardiovascular Agents
 Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013