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

This study is currently recruiting participants.
Verified January 2014 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: January 31, 2014
Last verified: January 2014

August 7, 2012
January 31, 2014
November 2012
August 2015   (final data collection date for primary outcome measure)
  • 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).

Fatigue [ Time Frame: Acutely at 1 week and 4 weeks ] [ Designated as safety issue: No ]
Determining if fatigue changes acutely between the two groups (Sildenafil, Tadalafil) at 1 week and 4 weeks.
Complete list of historical versions of study NCT01661595 on ClinicalTrials.gov Archive Site
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

Fractional Synthetic Rate [ Time Frame: Acutely - 1 day ] [ Designated as safety issue: No ]
Determining whether there is a difference between Sildenafil and Tadalafil at one day and at week 1.
Not Provided
Not Provided
 
The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue
The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue.

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.

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

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Fatigue
  • Drug: Sildenafil
    50 mg/day for 4 weeks
    Other Names:
    • Viagra
    • Revatio
  • Drug: tadalafil
    10 mg/day for 4 weeks.
    Other Names:
    • Cialis
    • Adcirca
  • Drug: Placebo
    Placebo 1 capsule per day for four weeks.
  • Active Comparator: Sildenafil
    50 mg/day Sildenafil Other Name: Viagra, Revatio
    Interventions:
    • Drug: Sildenafil
    • Drug: tadalafil
  • Active Comparator: tadalafil
    10 mg/day Tadalafil Other Name: Cialis, Adcirca
    Intervention: Drug: tadalafil
  • 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)
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
August 2016
August 2015   (final data collection date for primary outcome measure)

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).
Both
50 Years to 60 Years
Yes
Contact: Kathleen M. Randolph, B.S. (409) 772-8126 kmrandol@utmb.edu
Contact: William J. Durham, PhD (409) 772-8702 wjdurham@utmb.edu
United States
 
NCT01661595
12-153
Yes
The University of Texas, Galveston
The University of Texas, Galveston
Not Provided
Principal Investigator: Melinda Sheffield-Moore, PhD University of Texas Medical Branch, Galveston
The University of Texas, Galveston
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP