We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01661595
Recruitment Status : Completed
First Posted : August 9, 2012
Last Update Posted : December 4, 2015
Sponsor:
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:
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 or disease Intervention/treatment
Fatigue Drug: Sildenafil Drug: tadalafil Drug: Placebo

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue.
Study Start Date : November 2012
Primary Completion Date : June 2015
Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fatigue
U.S. FDA Resources

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Perceptual Fatigue [ Time Frame: Acutely at 1 week and 4 weeks ]

    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).


  2. Skeletal Muscle Fatigue [ Time Frame: Acutely at 1 week and 4 weeks ]

    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 :
  1. Fractional Synthesis Rate [ Time Frame: Acutely at 1 day and 1 week ]

    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




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01661595


Locations
United States, Texas
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0361
Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Investigators
Principal Investigator: Melinda Sheffield-Moore, PhD University of Texas Medical Branch, Galveston

Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT01661595     History of Changes
Other Study ID Numbers: 12-153
First Posted: August 9, 2012    Key Record Dates
Last Update Posted: December 4, 2015
Last Verified: December 2015

Keywords provided by The University of Texas Medical Branch, 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 Citrate
Tadalafil
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents