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

• ClinicalTrials.gov Identifier: NCT01661595
• Recruitment Status: Completed
• First Posted: August 9, 2012
• Results First Posted: July 17, 2018
• Last Update Posted: July 17, 2018
• Sponsor: The University of Texas Medical Branch, Galveston
• Information provided by (Responsible Party): The University of Texas Medical Branch, Galveston

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Fatigue
• Interventions: Drug: Sildenafil; Drug: tadalafil; Drug: Placebo
• Enrollment: 30

Participant Flow

Recruitment Details	Participants were recruited from the community via flyers and local postings.
Pre-assignment Details	30 subjects enrolled in this study. 6 subjects failed the screening and were withdrawn. 6 subjects chose to withdraw participation before the study began. 18 subjects began the study. 2 subjects were withdrawn during the study. 16 subjects completed the study.

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Period Title: Phase 1: Week 0-4
Started	5	4	5	4
Completed	4	4	5	4
Not Completed	1	0	0	0
Reason Not Completed
Adverse Event	1	0	0	0
Period Title: Phase 2: Week 5-8.
Started	4	4	5	4
Completed	4	4	4	4
Not Completed	0	0	1	0
Reason Not Completed
Protocol Violation	0	0	1	0

Baseline Characteristics

Arm/Group Title		Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil	Total
Arm/Group Description		Sildenafil (50mg/day) daily for weeks 0-4, then Placebo daily weeks 5-8.	Tadalafil (10mg/day) daily for weeks 0-4, then Placebo daily for weeks 5-8.	Placebo daily for weeks 0-4, then Sildenafil (50mg/day) daily for weeks 5-8.	Placebo daily for weeks 0-4, then Tadalafil (10mg/day) daily for weeks 5-8.	Total of all reporting groups
Overall Number of Baseline Participants		5	4	5	4	18
Baseline Analysis Population Description		30 subjects enrolled in this study. 6 subjects failed the screening and were withdrawn. 6 subjects chose to withdraw participation before the study began. 18 subjects began the study. 2 subjects were withdrawn during the study. 16 subjects completed the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	5 participants	4 participants	5 participants	4 participants	18 participants
		53.6 (4.16)	56 (1.41)	52.4 (1.51)	57.25 (2.99)	54.6 (3.22)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	5 participants	4 participants	5 participants	4 participants	18 participants
	Female	4 80.0%	4 100.0%	3 60.0%	2 50.0%	13 72.2%
	Male	1 20.0%	0 0.0%	2 40.0%	2 50.0%	5 27.8%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	5 participants	4 participants	5 participants	4 participants	18 participants
		5 100.0%	4 100.0%	5 100.0%	4 100.0%	18 100.0%

Outcome Measures

1. Primary Outcome

Title	Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Placebo
Description	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.
Time Frame	after 4 weeks of placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalafil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	59.69 (33.71)	42.07 (5.19)	67.17 (26.87)	63.24 (8.34)

2. Primary Outcome

Title	Skeletal Muscle Fatigue as Measured by Biodex 4 Pro After 4 Weeks of Active Drug
Description	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.
Time Frame	after 4 weeks of active drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil / Placebo	Tadalafil / Placebo	Placebo / Sildenafil	Placebo / Tadalafil
Arm/Group Description:	50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	60.90 (35.60)	42.48 (6.30)	62.68 (24.88)	63.25 (15.12)

3. Primary Outcome

Title	Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Placebo
Description	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.
Time Frame	after 4 weeks of placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil / Placebo	Tadalafil / Placebo	Placebo / Sildenafil	Placebo / Tadalafil
Arm/Group Description:	50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.33 (1.53)	2.5 (0.58)	7.0 (1.83)	4.75 (0.96)

4. Primary Outcome

Title	Exercised Induced Fatigability as Measured by Fatigue Rating Scale After 4 Weeks of Active Drug
Description	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.
Time Frame	after 4 weeks of active drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil / Placebo	Tadalafil / Placebo	Placebo / Sildenafil	Placebo / Tadalafil
Arm/Group Description:	50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 0-4. Placebo for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 0-4. Placebo for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 50 mg/day Sildenafil: (Other Name: Viagra, Revatio) for weeks 5-8. Sildenafil: 50 mg/day for 4 weeks Placebo: Placebo 1 capsule per day for four weeks.	Placebo for weeks 0-4. 10 mg/day Tadalafil: (Other Name: Cialis, Adcirca) for weeks 5-8. tadalafil: 10 mg/day for 4 weeks. Placebo: Placebo 1 capsule per day for four weeks.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: units on a scale
	4.5 (2.38)	3.5 (1.73)	5.25 (4.27)	6.0 (1.83)

5. Secondary Outcome

Title	Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo
Description	Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was 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.
Time Frame	after 4 weeks of placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	145.86 (97.73)	104.17 (23.66)	149.14 (62.67)	148.34 (47.26)

6. Secondary Outcome

Title	Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug.
Description	Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength was 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.
Time Frame	after 4 weeks of active drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	140.09 (82.29)	110.39 (21.26)	133.81 (58.04)	139.96 (50.47)

7. Secondary Outcome

Title	Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Placebo.
Description	Isokinetic strength (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. 1 set of 3 contractions were performed at 100% force. Isokinetic strength 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.
Time Frame	after 4 weeks of placebo

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	105.15 (49.46)	78.59 (10.25)	117.71 (39.86)	111.67 (23.43)

8. Secondary Outcome

Title	Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 After 4 Weeks of Active Drug
Description	Isokinetic strength (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. 1 set of 3 contractions were performed at 100% force. Isokinetic strength 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.
Time Frame	after 4 weeks of active drug

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: Newton-Meters
	106.79 (49.69)	79.33 (11.69)	116.48 (37.83)	114.75 (36.49)

9. Secondary Outcome

Title	Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.
Description	Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	5	4	5	4
Mean (Standard Deviation); Unit of Measure: kilograms
	44.60 (11.62)	41.43 (4.72)	49.93 (10.63)	54.45 (14.28)

10. Secondary Outcome

Title	Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.
Description	Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	5	4
Mean (Standard Deviation); Unit of Measure: kilograms
	46.29 (14.40)	41.02 (4.05)	50.61 (10.67)	54.85 (14.71)

11. Secondary Outcome

Title	Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.
Description	Lean Body Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: kilograms
	46.22 (14.68)	40.76 (4.38)	52.09 (10.03)	55.10 (14.42)

12. Secondary Outcome

Title	Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 0.
Description	Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	5	4	5	4
Mean (Standard Deviation); Unit of Measure: kilograms
	32.35 (11.40)	37.21 (6.81)	32.72 (5.92)	32.10 (6.90)

13. Secondary Outcome

Title	Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 4.
Description	Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	5	4
Mean (Standard Deviation); Unit of Measure: kilograms
	33.16 (12.42)	37.12 (6.35)	32.30 (5.55)	32.47 (7.08)

14. Secondary Outcome

Title	Fat Mass as Measured by Dual Energy X-ray Absorptiometry at Week 8.
Description	Fat Mass is calculated from a whole body scan measured on a dual energy x-ray absorptiometry.
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: kilograms
	33.60 (12.51)	37.02 (6.21)	32.40 (5.83)	32.79 (7.12)

15. Secondary Outcome

Title	Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Placebo
Description	Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed 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.
Time Frame	after 4 weeks of placebo

Outcome Measure Data

Analysis Population Description

1 subject did not complete the walking test

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	3	4	4	4
Mean (Standard Deviation); Unit of Measure: meters
	203.82 (30.51)	189.79 (38.12)	198.41 (14.04)	202.80 (37.84)

16. Secondary Outcome

Title	Walking Distance at 100% Effort as Measured by Walking Test After 4 Weeks of Active Drug
Description	Walking performance will be assessed during 2 minutes of walking in long corridor hallways. Subjects will be asked to walk at 100% effort (as quickly as they can safely walk without running) for 2 minutes. Distance traveled for the 2 minutes will be recorded. The walking test will be completed 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.
Time Frame	after 4 weeks of active drug

Outcome Measure Data

Analysis Population Description

1 subject did not complete the walking test.

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	3	4	4	4
Mean (Standard Deviation); Unit of Measure: meter
	197.01 (32.72)	178.56 (17.84)	200.19 (13.99)	203.46 (31.11)

17. Secondary Outcome

Title	Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 0
Description	Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
Time Frame	Week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: scores on a scale
	9.66 (19.55)	-7.5 (5.45)	-8 (3.61)	-3.75 (9.54)

18. Secondary Outcome

Title	Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 4
Description	Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

1 subject did not complete the week 4 MFSI questionnaire

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	3	4	4
Mean (Standard Deviation); Unit of Measure: scores on a scale
	6.33 (26.08)	-3.33 (10.97)	-6.33 (2.31)	-3.5 (12.66)

19. Secondary Outcome

Title	Perceptual Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form Total Score at Week 8
Description	Fatigue symptoms will be measured using the 30-item Multidimensional Fatigue Symptom Inventory - Short Form, a validated measure that yields one overall score of total fatigue calculated using five sub scales (general, physical, emotional, mental, vigor). With the exception of the vigor sub scale, higher scores indicate greater fatigue. Total fatigue score is calculated by summing the sub categories (general, physical, emotional and mental) and subtracting vigor. Total scores range from -24 to 96, with a higher score indicating more fatigue.
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: scores on a scale
	9.67 (19.09)	3.25 (27.54)	-9.67 (6.81)	-9.25 (1.26)

20. Other Pre-specified Outcome

Title	Hemoglobin Level at Week 0
Description	Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
Time Frame	week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: g/dL
	13.42 (0.97)	12.78 (0.71)	12.4 (0.53)	13.05 (0.90)

21. Other Pre-specified Outcome

Title	Hemoglobin Level Measured at Week 4
Description	Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
Time Frame	week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: g/dL
	13.05 (0.49)	12.03 (0.43)	12.6 (0.37)	13.2 (0.47)

22. Other Pre-specified Outcome

Title	Hemoglobin Level Measured at Week 8
Description	Hemoglobin was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 11.6 - 15.0 g/dL.
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: g/dL
	13.55 (0.35)	11.97 (0.76)	12.5 (0.08)	12.95 (1.17)

23. Other Pre-specified Outcome

Title	Hematocrit Level Measured at Week 0
Description	Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
Time Frame	week 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: percent of red blood cells
	39.53 (2.16)	38.55 (1.42)	37.25 (2.07)	31.88 (13.09)

24. Other Pre-specified Outcome

Title	Hematocrit Level Was Measured at 4 Weeks
Description	Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: percent of red blood cells
	39.08 (0.84)	37.38 (0.82)	38.13 (0.77)	39.1 (1.81)

25. Other Pre-specified Outcome

Title	Hematocrit Level Measured at Week 8
Description	Hematocrit was measured by University of Texas Medical Branch Clinical Laboratory. Normal ranges are 35.7 - 45.2%.
Time Frame	week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sildenafil, Then Placebo	Tadalfil, Then Placebo	Placebo, Then Sildenafil	Placebo, Then Tadalafil
Arm/Group Description:	Sildenafil daily (50mg/day) for weeks 0-4. Then Placebo daily for weeks 5-8.	Tadalafil (10mg/day) for week 0-4. Then Placebo daily for week 5-8.	Placebo daily for weeks 0-4. Then Sildenafil daily (50mg/day) for weeks 5-8.	Placebo for week 0-4, then Tadalafil (10mg/day) for week 5-8.
Overall Number of Participants Analyzed	4	4	4	4
Mean (Standard Deviation); Unit of Measure: percent of red blood cells
	40.38 (0.44)	36.6 (1.94)	38.1 (1.19)	38.4 (3.24)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Sildenafil		Tadalfil		Placebo
Arm/Group Description	Sildenafil (50mg/day) daily for 4 weeks.		Tadalafil (10mg/day) daily for 4 weeks.		Placebo daily for week 4 weeks.
All-Cause Mortality
	Sildenafil		Tadalfil		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/10 (0.00%)		0/8 (0.00%)		0/18 (0.00%)
Serious Adverse Events
	Sildenafil		Tadalfil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0.00%)		0/8 (0.00%)		0/18 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Sildenafil		Tadalfil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/10 (20.00%)		0/8 (0.00%)		0/18 (0.00%)
General disorders
Syncope [1]	1/10 (10.00%)	1	0/8 (0.00%)	0	0/18 (0.00%)	0
Skin and subcutaneous tissue disorders
Redness at site of muscle biopsy	1/10 (10.00%)	1	0/8 (0.00%)	0	0/18 (0.00%)	0
[1] Syncope following administration of Sildenafil 50mg.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Melinda Sheffield-Moore
• Organization: University of Texas Medical Branch
• Phone: 409-772-8707
• EMail: melmoore@utmb.edu

• Responsible Party: The University of Texas Medical Branch, Galveston
• ClinicalTrials.gov Identifier: NCT01661595
• Other Study ID Numbers: 12-153
• First Submitted: August 7, 2012
• First Posted: August 9, 2012
• Results First Submitted: April 24, 2018
• Results First Posted: July 17, 2018
• Last Update Posted: July 17, 2018