The Effect of Sildenafil and Tadalafil on Skeletal Muscle and Perceptual Fatigue.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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).
- •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).
研究组 & 干预措施
Sildenafil / Placebo
50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.
干预措施: Sildenafil (Drug)
Sildenafil / Placebo
50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8.
干预措施: Placebo (Drug)
Tadalafil / Placebo
10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.
干预措施: tadalafil (Drug)
Tadalafil / Placebo
10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8.
干预措施: Placebo (Drug)
Placebo / Sildenafil
Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.
干预措施: Sildenafil (Drug)
Placebo / Sildenafil
Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8.
干预措施: Placebo (Drug)
Placebo / Tadalafil
Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.
干预措施: tadalafil (Drug)
Placebo / Tadalafil
Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8.
干预措施: Placebo (Drug)
结局指标
主要结局
Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo
时间窗: 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.
Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug
时间窗: 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.
Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo
时间窗: 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.
Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug
时间窗: 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.
次要结局
- Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.(week 4)
- Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.(week 8)
- 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)
- Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.(week 8)
- Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo(after 4 weeks of placebo)
- Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8(week 8)
- Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.(week 0)
- Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0(Week 0)
- Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.(week 0)
- Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.(week 4)
- Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug(after 4 weeks of active drug)
- Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4(week 4)