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

NCT01661595 | Completed Results DMC

• 1 other identifier: 12-153
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Fatigue

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo

  Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.

  after 4 weeks of placebo

• Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug

  Isokinetic Fatigue Measure (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 50 contractions were performed at 100% force, one contraction every second. Isokinetic fatigue will be measured at week 4 and week 8. Depending on grouping, the week 4 and week 8 measures may be placebo or active drug. Data will be reported as after 4 weeks of placebo or after 4 weeks of active drug. Data is presented as mean maximum force over all 50 kicks.

  after 4 weeks of active drug

• Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo

  The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test after 4 weeks of placebo. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.

  after 4 weeks of placebo

• Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug

  The fatigue rating scale is a scale from 0 to 10 with 0 being no fatigue at all and 10 being the worst fatigue the subject can imagine. The subject is asked to rate their level of fatigue in their leg. This test was performed before and immedicately after the Biodex leg fatigue test. Data is presented as change in scale from pre fatigue test to post fatigue test, with a higher score indicating a greater level of fatigue.

  after 4 weeks of active drug

Secondary Outcomes (15)

• Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo

  after 4 weeks of placebo

• Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.

  after 4 weeks of active drug

• Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.

  after 4 weeks of placebo

• Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug

  after 4 weeks of active drug

• Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.

  week 0

Other Outcomes (6)

• Hemoglobin Level at Week 0

  week 0

• Hemoglobin Level Measured at Week 4

  week 4

• Hemoglobin Level Measured at Week 8

  week 8

Study Arms (4)

Sildenafil / Placebo

ACTIVE COMPARATOR

50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.

Drug: Sildenafil; Drug: Placebo

Tadalafil / Placebo

ACTIVE COMPARATOR

10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.

Drug: tadalafil; Drug: Placebo

Placebo / Sildenafil

ACTIVE COMPARATOR

Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.

Drug: Sildenafil; Drug: Placebo

Placebo / Tadalafil

ACTIVE COMPARATOR

Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.

Drug: tadalafil; Drug: Placebo

Interventions

Sildenafil DRUG

50 mg/day for 4 weeks

Also known as: Viagra, Revatio

Placebo / Sildenafil; Sildenafil / Placebo

tadalafil DRUG

10 mg/day for 4 weeks.

Also known as: Cialis, Adcirca

Placebo / Tadalafil; Tadalafil / Placebo

Placebo DRUG

Placebo 1 capsule per day for four weeks.

Placebo / Sildenafil; Placebo / Tadalafil; Sildenafil / Placebo; Tadalafil / Placebo

Eligibility Criteria

• Age: 50 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 50-60 years of age
• Ability to sign consent form (score\>23 on the 30-item Mini Mental Status examination, MMSE)
• Stable body weight for at least three months.

You may not qualify if:

• 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).
• Pregnancy
• Significant heart, liver, kidney, blood or respiratory disease.
• Peripheral vascular disease.
• Diabetes mellitus or other untreated endocrine disease.
• Active cancer
• Use of nitrates.
• Recent (within 6 months) treatment with anabolic steroids, or corticosteroids.
• Alcohol or drug abuse.
• Severe depression (\>5 on the 15-item Geriatric Depression Scale, GDS).
• Cardiac abnormalities such as cardiac shunt or previously diagnosed pulmonary hypertension.
• 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).

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead

Study Sites (1)

University of Texas Medical Branch

Galveston, Texas, 77555-0361, United States

Location

MeSH Terms

Conditions

Fatigue

Interventions

Sildenafil Citrate; Tadalafil

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carbolines; Pyridines; Indole Alkaloids; Indoles; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Melinda Sheffield-Moore
• Organization: University of Texas Medical Branch

melmoore@utmb.edu

409-772-8707

Study Officials

• Melinda Sheffield-Moore, PhD

  University of Texas Medical Branch, Galveston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects were assigned to one of 4 arms: 1. Sildenafil (50mg/day) for weeks 0-4. Placebo for weeks 5-8. 2. Tadalafil (10mg/day) for weeks 0-4. Placebo for weeks 5-8. 3. Placebo for weeks 0-4. Sildenafil (50mg/day) for weeks 5-8. 4. Placebo for weeks 0-4. Tadalafil (10mg/day) for weeks 5-8.

Study Record Dates

• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 17, 2018
• Results First Posted: July 17, 2018

Record last verified: 2018-04

Locations

US (1)