Duchenne Muscular DystrophyPhase 2NCT06290713
Vasodilator and Exercise Study for DMD (VASO-REx)
A Phase 2 study testing Tadalafil and Exercise Training in people with Duchenne Muscular Dystrophy and Duchenne Disease, run by University of Florida at 1 site in United States.
Trial summary
Examining two strategies as potential adjuvant therapies for Duchenne muscular dystrophy (DMD); aerobic exercise training (to induce adaptations in skeletal muscle and improve cardiovascular health) and tadalafil, an FDA-approved vasodilator (to optimize blood flow and muscle perfusion which is impaired and often… Read more about this study
- Who is it for?
- Ages 6 years and older, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy, Duchenne Disease, Muscular Dystrophy
- What is being tested?
- Tadalafil and Exercise Training
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2024to Nov 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of DMD confirmed by genetic report
- Minimum entry age of 6.0 years old
- Ambulatory
- On stable glucocorticoid regimen (for > 3 months)
Who cannot join
- Contraindication to a Magnetic resonance Imaging examination (e.g. severe claustrophobia, magnetic implants, unable/unwilling to perform test)
- Presence of unstable medical problems, including severe cardiomyopathy, left ventricular ejection fraction <45%, cardiac conduction abnormalities as evidenced on ECG, uncontrolled seizure disorder, uncontrolled hypo or hypertension
- Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g., myasthenia gravis, endocrine disorder, mitochondrial disease)
- Presence of a secondary condition leading to developmental delay or impaired motor control (e.g., cerebral palsy) or previous history of unprovoked rhabdomyolysis
- Contraindications to phosphodiesterase 5 inhibitors (use of nitrates, alpha-adrenergic blockers, other phosphodiesterase 5 inhibitors) or other medications known to modulate blood flow or muscle metabolism
- Participation in currently approved FDA trials or other investigational clinical trials during the period of the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Florida Clinical and Translational Research Building
Gainesville, Florida, 32603
About this study
Official title: Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy (VASO-REx Study)
Examining two strategies as potential adjuvant therapies for Duchenne muscular dystrophy (DMD); aerobic exercise training (to induce adaptations in skeletal muscle and improve cardiovascular health) and tadalafil, an FDA-approved vasodilator (to optimize blood flow and muscle perfusion which is impaired and often overlooked in DMD). Target: improved muscle function, vascular health, and DMD treatment.
Read the detailed description
Duchenne muscular dystrophy (DMD) is characterized by rapid muscle deterioration, mitochondrial and vascular impairments, resulting in premature loss of ambulation and mortality. Disease-modifying therapeutics are emerging and although they are expected to improve muscle function and daily activity in boys with DMD, most are not designed to correct the vascular impairment. This impairment is due to the lack of restoration of neuronal nitric oxide synthase signaling, which is crucial for vasodilation during and after exercise. The investigators believe limitations in study design were responsible for the lack of efficacy. Therefore, this study combines tadalafil with aerobic exercise to necessitate increased blood flow and activate the drug.
This Exploratory Clinical Trial will assess two potential adjuvant therapies for ambulatory boys with DMD (6 years and older): 1) aerobic exercise training and 2) tadalafil, an FDA-approved vasodilator drug. Preclinical and clinical data, including recent findings from the principal investigator's lab, support the use of these strategies and their potential to benefit muscle perfusion, fatigue, and quality of life.
The study will first test for drug responsiveness (increase in muscle oxygenation) after a single dose. Drug-responsive boys with DMD will be randomized to a 6-month intervention of daily tadalafil or placebo, combined with structured cycle exercise training. Participants will receive exercise-related equipment for use at home and be monitored by the research team via video. The study will quantify the intervention's impact on vascular impairment, muscle pathophysiology (inflammation, fat accumulation, mitochondrial dysfunction), exertional fatigue, and cycling performance.
Our findings are expected to yield:
- Criteria to identify DMD patients most likely to benefit from tadalafil as adjuvant therapy.
- Evidence of a powerful synergy between drug impact and exercise training in DMD.
- Conditions
- Duchenne Muscular Dystrophy, Duchenne Disease, Muscular Dystrophy, Muscular Dystrophy in Children, Vasodilation, Exercise
- Being tested
- Tadalafil, Placebo, Exercise Training
- Keywords
- DMD, Tadalafil, Drug and Exercise Intervention, Treatment Strategy
- Medical subject headings
- Muscular Dystrophy, Duchenne, Tabes Dorsalis, Muscular Dystrophies, Aneurysm, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.
PlaceboDrug
Patients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions.
Exercise TrainingOther
The home-based cycling exercise training program is designed to improve muscle strength and endurance. Participants will engage in individualized exercise sessions up to four times per week, lasting up to 40 minutes each. Live video and heart rate monitoring will ensure proper exercise performance and allow for adjustments to the program throughout the study. The participants will receive the exercise equipment for use at home.
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil and Exercise Arm | Experimental | Participants receive tadalafil weight-dependent dosage to take daily for 6 months (26 weeks). Receives: Drug: Tadalafil; Other: Exercise Training |
| Placebo and Exercise Arm | Placebo comparator | Participants receive a tadalafil placebo tablet matching the tadalafil weight-dependent dosage to take daily for 6 months (26 weeks). Receives: Drug: Placebo; Other: Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular responsiveness after muscle contraction to a single dose of tadalafil.
Responsiveness will be determined by an increase in post-contractile muscle oxygenation using MRI-Blood Oxygen Level Dependent (BOLD) responses after dosing compared to before. Study participants demonstrating an increase (>50%) in post-contractile BOLD after tadalafil will be enrolled into Aim 2 of this study.
Measured: up to 4 weeks after the completion of Visits 1 and 2 of Aim 1.
Cycling time to fatigue
The study will assess the impact of tadalafil on exercise performance and fatigue resistance compared to placebo. Participants will undergo a maximal effort cycling test before and after the intervention period. The time it takes for participants to reach exhaustion (TTE) will be recorded as the primary outcome measure.
Measurement: Time to exhaustion (TTE) during a maximal effort cycling test on a recumbent, stationary ergometer. This test will quantify fatigue resistance by measuring the duration participants can sustain maximal effort cycling.
Measured: Baseline and 6 month follow-up visits of Aim 2.
Secondary outcomes (21)
Quadriceps muscle Fat Fraction
This outcome serves as a measure of disease severity. This measure is a sensitive and reproducible biomarker of DMD muscle pathology.
Measured: Aim 1 and Aim 2 (baseline and 6 month follow-up)
Metabolic recovery
The rate of phosphocreatine resynthesis after leg exercise will be quantified and serves as index of skeletal muscle mitochondrial oxidative capacity. (Part of Aim 2 of the study).
Measured: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Peak aerobic capacity (VO2max)
Patients will undergo cycling exercise at submaximal and peak workloads to quantify peak aerobic capacity, ventilation.
Peak Oxygen Uptake (VO2max): This measure quantifies the maximum amount of oxygen the body can utilize during exercise, assessed through maximal cycling effort in a CPET. It serves as a primary indicator of overall cardiovascular and aerobic fitness.
Peak aerobic capacity: VO2max reflects the maximum oxygen utilization capacity, indicating overall cardiovascular fitness.
Measured: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Minute Ventilation (VE)
Minute Ventilation (VE): This measure reflects the total volume of air breathed per minute during exercise, assessed throughout the CPET. Evaluating VE at various workloads provides insights into respiratory efficiency and potential limitations during exercise.
Respiratory efficiency: VE and VE/VO2 assess how well the body utilizes oxygen during exercise, revealing potential respiratory limitations.
Measured: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Ventilatory Equivalent for Oxygen (VE/VO2)
Ventilatory Equivalent for Oxygen (VE/VO2): This ratio compares ventilation to oxygen uptake, calculated throughout the CPET. It indicates the efficiency of oxygen utilization during exercise and potential respiratory limitations.
Respiratory efficiency: VE and VE/VO2 assess how well the body utilizes oxygen during exercise, revealing potential respiratory limitations.
Measured: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Gas Exchange Threshold (GET)
Gas Exchange Threshold (GET): This point during exercise marks the transition from predominantly aerobic to anaerobic metabolism, identified through changes in blood lactate levels and other CPET parameters. Analyzing GET helps assess exercise tolerance and potential for improvement.
Exercise tolerance and fatigue: GET and W at AT pinpoint the intensity at which fatigue and performance decline become significant, offering insights into exercise limitations and potential for improvement.
Measured: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Workload at Anaerobic Threshold (W at AT)
Workload at Anaerobic Threshold (W at AT): This measure, derived from the CPET, quantifies the power output at which anaerobic metabolism significantly contributes to energy production. It reflects exercise intensity at which fatigue and performance decline become prominent.
Exercise tolerance and fatigue: GET and W at AT pinpoint the intensity at which fatigue and performance decline become significant, offering insights into exercise limitations and potential for improvement.
Measured: Through study completion, an average of 3 years.
The 100-meter timed test (100m)
The 100m is a fixed distance test of maximal performance and will be completed according to published guidelines.
Measured: Through study completion, an average of 3 years.
the North Star Ambulatory Assessment (NSAA)
The North Star Ambulatory Assessment (NSAA) is a 17-item rating scale that is used to measure physical function and motor abilities in ambulatory boys with DMD and is increasingly being used in clinical trials as an overall measure of physical function.
Measured: Through study completion, an average of 3 years.
The 4-stair climb
The time to ascend 4-stairs is a strength-measure. The patient is instructed to climb four standard steps (six inches in height each) with two handrails as fast as safely possible, using the rails if needed.
Measured: Through study completion, an average of 3 years.
The Physical activity questionnaire (PAQ-C)
The PAQ-C is a self-administered, 7-day recall instrument developed to assess general levels of physical activity throughout the elementary school year for students in grades 4 to 8 and approximately 8 to 14 years, with high validity. Although reliability is considered to be moderate, other physical activity questionnaires are less reliable. Results will be correlated with indices of disease severity and tadalafil responsiveness.
Measured: Through study completion, an average of 3 years.
Pulmonary function testing - vital capacity (FVC)
Measurement: FVC, measured using a standard spirometer according to American Thoracic Society guidelines. This is the maximum amount of air an individual can forcefully exhale after a full inhalation.
Significance: FVC reflects the total lung capacity and is a key indicator of overall lung volume and function. It can help identify restrictive lung diseases, where lung volume is limited, and track respiratory health changes over time.
Measured: Through study completion, an average of 3 years.
Pulmonary function testing - forced expiratory volume in 1 second (FEV1)
Measurement: FEV1, measured using a standard spirometer according to American Thoracic Society guidelines. This is the amount of air forcefully exhaled in the first second of a maximal exhalation after a full inhalation.
Significance: FEV1 reflects the efficiency of airflow from the lungs and is sensitive to obstructive lung diseases, like asthma and Chronic Obstructive Pulmonary Disease (COPD), where airflow is impaired.
Measured: Through study completion, an average of 3 years.
Neurology Quality of Life (NeuroQoL) pediatric lower extremity function
Questionnaire used to measure patient-reported outcomes of intervention impact.
Measured: Through study completion, an average of 3 years.
Patient Reported Outcomes Measurement Information System (PROMIS) pediatric fatigue
Questionnaire used to measure patient-reported outcomes of intervention impact.
Measured: Through study completion, an average of 3 years.
PROMIS parent proxy for physical activity
Questionnaire used to measure patient's parent-reported outcomes of intervention impact.
Measured: Through study completion, an average of 3 years.
PROMIS pediatric physical activity
Questionnaire used to measure patient's parent-reported outcomes of intervention impact.
Measured: Through study completion, an average of 3 years.
Physical Activity Monitoring - Daily Step Rate
Measurement: Total number of steps taken per day, assessed using the Actigraph activity monitor.
Measured: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in Low-Level Activity
Measurement: Total time spent in low-intensity physical activity per day, as defined by Actigraph criteria.
Measured: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in Moderate-Level Activity
Measurement: Total time spent in moderate-intensity physical activity per day, as defined by Actigraph criteria.
Measured: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in High-Level Activity
Measurement: Total time spent in high-intensity physical activity per day, as defined by Actigraph criteria.
Measured: Through study completion, an average of 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2024
- Study start5 Jun 2024
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (66)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are assigned to receive interventions based on their completion and results of Aim 1 (responsiveness to study drug). If participants are found to be Tadalafil-responsive after one dose, they will be included in Aim 2 of the study and will be asked to participate in the double-blinded, randomized, placebo-controlled longitudinal medication \& exercise 6-month study program.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Tanja Taivassalo, Ph.D., Principal investigator, University of Florida, College of Medicine, Department of Physiology and Aging
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06290713
- Sponsor's protocol ID
- IRB202301491
- Other IDs
- 1R21AR079755-01, PRO00050023
- Status last verified
- Apr 2026
- First submitted
- 9 Feb 2024
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Lopez C, Taivassalo T, Berru MG, Saavedra A, Rasmussen HC, Batra A, Arora H, Roetzheim AM, Walter GA, Vandenborne K, Forbes SC. Postcontractile blood oxygenation level-dependent (BOLD) response in Duchenne muscular dystrophy. J Appl Physiol (1985). 2021 Jul 1;131(1):83-94. doi: 10.1152/japplphysiol.00634.2020. Epub 2021 May 20.
PubMed 34013753Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, Iammarino MA, Alfano LN, Nicholl A, Al-Zaidy S, Lewis S, Church K, Shell R, Cripe LH, Potter RA, Griffin DA, Pozsgai E, Dugar A, Hogan M, Rodino-Klapac LR. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. 2020 Sep 1;77(9):1122-1131. doi: 10.1001/jamaneurol.2020.1484.
PubMed 32539076Harper SQ. Molecular dissection of dystrophin identifies the docking site for nNOS. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):387-8. doi: 10.1073/pnas.1220256110. Epub 2012 Dec 31. No abstract available.
PubMed 23277550Duan D. Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy. Mol Ther. 2018 Oct 3;26(10):2337-2356. doi: 10.1016/j.ymthe.2018.07.011. Epub 2018 Jul 17.
PubMed 30093306Percival JM, Adamo CM, Beavo JA, Froehner SC. Evaluation of the therapeutic utility of phosphodiesterase 5A inhibition in the mdx mouse model of duchenne muscular dystrophy. Handb Exp Pharmacol. 2011;(204):323-44. doi: 10.1007/978-3-642-17969-3_14.
PubMed 21695647Thomas GD. Functional muscle ischemia in Duchenne and Becker muscular dystrophy. Front Physiol. 2013 Dec 18;4:381. doi: 10.3389/fphys.2013.00381.
PubMed 24391598Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, Campbell KP. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008 Nov 27;456(7221):511-5. doi: 10.1038/nature07414. Epub 2008 Oct 26.
PubMed 18953332Sheffield-Moore M, Wiktorowicz JE, Soman KV, Danesi CP, Kinsky MP, Dillon EL, Randolph KM, Casperson SL, Gore DC, Horstman AM, Lynch JP, Doucet BM, Mettler JA, Ryder JW, Ploutz-Snyder LL, Hsu JW, Jahoor F, Jennings K, White GR, McCammon SD, Durham WJ. Sildenafil increases muscle protein synthesis and reduces muscle fatigue. Clin Transl Sci. 2013 Dec;6(6):463-8. doi: 10.1111/cts.12121. Epub 2013 Oct 29.
PubMed 24330691Nelson MD, Rader F, Tang X, Tavyev J, Nelson SF, Miceli MC, Elashoff RM, Sweeney HL, Victor RG. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology. 2014 Jun 10;82(23):2085-91. doi: 10.1212/WNL.0000000000000498. Epub 2014 May 7.
PubMed 24808022Victor RG, Sweeney HL, Finkel R, McDonald CM, Byrne B, Eagle M, Goemans N, Vandenborne K, Dubrovsky AL, Topaloglu H, Miceli MC, Furlong P, Landry J, Elashoff R, Cox D; Tadalafil DMD Study Group. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology. 2017 Oct 24;89(17):1811-1820. doi: 10.1212/WNL.0000000000004570. Epub 2017 Sep 29.
PubMed 28972192Hoffman EP. Pharmacotherapy of Duchenne Muscular Dystrophy. Handb Exp Pharmacol. 2020;261:25-37. doi: 10.1007/164_2019_256.
PubMed 31375923Mah JK. An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy. Methods Mol Biol. 2018;1687:3-17. doi: 10.1007/978-1-4939-7374-3_1.
PubMed 29067652Verhaart IEC, Aartsma-Rus A. Therapeutic developments for Duchenne muscular dystrophy. Nat Rev Neurol. 2019 Jul;15(7):373-386. doi: 10.1038/s41582-019-0203-3.
PubMed 31147635Ramos JN, Hollinger K, Bengtsson NE, Allen JM, Hauschka SD, Chamberlain JS. Development of Novel Micro-dystrophins with Enhanced Functionality. Mol Ther. 2019 Mar 6;27(3):623-635. doi: 10.1016/j.ymthe.2019.01.002. Epub 2019 Feb 1.
PubMed 30718090Lai Y, Thomas GD, Yue Y, Yang HT, Li D, Long C, Judge L, Bostick B, Chamberlain JS, Terjung RL, Duan D. Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J Clin Invest. 2009 Mar;119(3):624-35. doi: 10.1172/JCI36612. Epub 2009 Feb 23.
PubMed 19229108
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy (VASO-REx Study)
- ClinicalTrials.gov ID
- NCT06290713
- Acronym / sponsor ID
- IRB202301491
- Conditions
- Duchenne Muscular Dystrophy, Duchenne Disease, Muscular Dystrophy, Muscular Dystrophy in Children, Vasodilation, Exercise
- Keywords
- DMD, Tadalafil, Drug and Exercise Intervention, Treatment Strategy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 5 Jun 2024 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 4 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Examining two strategies as potential adjuvant therapies for Duchenne muscular dystrophy (DMD); aerobic exercise training (to induce adaptations in skeletal muscle and improve cardiovascular health) and tadalafil, an FDA-approved vasodilator (to optimize blood flow and muscle perfusion which is impaired and often overlooked in DMD). Target: improved muscle function, vascular health, and DMD treatment.
Detailed description
Duchenne muscular dystrophy (DMD) is characterized by rapid muscle deterioration, mitochondrial and vascular impairments, resulting in premature loss of ambulation and mortality. Disease-modifying therapeutics are emerging and although they are expected to improve muscle function and daily activity in boys with DMD, most are not designed to correct the vascular impairment. This impairment is due to the lack of restoration of neuronal nitric oxide synthase signaling, which is crucial for vasodilation during and after exercise. The investigators believe limitations in study design were responsible for the lack of efficacy. Therefore, this study combines tadalafil with aerobic exercise to necessitate increased blood flow and activate the drug.
This Exploratory Clinical Trial will assess two potential adjuvant therapies for ambulatory boys with DMD (6 years and older): 1) aerobic exercise training and 2) tadalafil, an FDA-approved vasodilator drug. Preclinical and clinical data, including recent findings from the principal investigator's lab, support the use of these strategies and their potential to benefit muscle perfusion, fatigue, and quality of life.
The study will first test for drug responsiveness (increase in muscle oxygenation) after a single dose. Drug-responsive boys with DMD will be randomized to a 6-month intervention of daily tadalafil or placebo, combined with structured cycle exercise training. Participants will receive exercise-related equipment for use at home and be monitored by the research team via video. The study will quantify the intervention's impact on vascular impairment, muscle pathophysiology (inflammation, fat accumulation, mitochondrial dysfunction), exertional fatigue, and cycling performance.
Our findings are expected to yield:
- Criteria to identify DMD patients most likely to benefit from tadalafil as adjuvant therapy.
- Evidence of a powerful synergy between drug impact and exercise training in DMD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are assigned to receive interventions based on their completion and results of Aim 1 (responsiveness to study drug). If participants are found to be Tadalafil-responsive after one dose, they will be included in Aim 2 of the study and will be asked to participate in the double-blinded, randomized, placebo-controlled longitudinal medication \& exercise 6-month study program.
| Arm | Type | Receives |
|---|---|---|
| Tadalafil and Exercise Arm | Experimental | Drug: Tadalafil, Other: Exercise TrainingParticipants receive tadalafil weight-dependent dosage to take daily for 6 months (26 weeks). |
| Placebo and Exercise Arm | Placebo comparator | Drug: Placebo, Other: Exercise TrainingParticipants receive a tadalafil placebo tablet matching the tadalafil weight-dependent dosage to take daily for 6 months (26 weeks). |
Who may qualify
- Ages
- 6 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of DMD confirmed by genetic report
- Minimum entry age of 6.0 years old
- Ambulatory
- On stable glucocorticoid regimen (for > 3 months)
Key exclusion criteria (6 listed)
- Contraindication to a Magnetic resonance Imaging examination (e.g. severe claustrophobia, magnetic implants, unable/unwilling to perform test)
- Presence of unstable medical problems, including severe cardiomyopathy, left ventricular ejection fraction <45%, cardiac conduction abnormalities as evidenced on ECG, uncontrolled seizure disorder, uncontrolled hypo or hypertension
- Presence of a secondary condition that impacts muscle function or muscle metabolism (e.g., myasthenia gravis, endocrine disorder, mitochondrial disease)
- Presence of a secondary condition leading to developmental delay or impaired motor control (e.g., cerebral palsy) or previous history of unprovoked rhabdomyolysis
- Contraindications to phosphodiesterase 5 inhibitors (use of nitrates, alpha-adrenergic blockers, other phosphodiesterase 5 inhibitors) or other medications known to modulate blood flow or muscle metabolism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TadalafilPatients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions. | Drug | Tadalafil and Exercise Arm |
| PlaceboPatients will be given either the intervention medication or a placebo (double-blinded, randomized trial) and will be asked to take the medication every day for 6 months in conjunction with weekly exercise sessions. | Drug | Placebo and Exercise Arm |
| Exercise TrainingThe home-based cycling exercise training program is designed to improve muscle strength and endurance. Participants will engage in individualized exercise sessions up to four times per week, lasting up to 40 minutes each. Live video and heart rate monitoring will ensure proper exercise performance and allow for adjustments to the program throughout the study. The participants will receive the exercise equipment for use at home. | Other | Placebo and Exercise Arm, Tadalafil and Exercise Arm |
Primary outcome
Vascular responsiveness after muscle contraction to a single dose of tadalafil.
Time frame: up to 4 weeks after the completion of Visits 1 and 2 of Aim 1.
Responsiveness will be determined by an increase in post-contractile muscle oxygenation using MRI-Blood Oxygen Level Dependent (BOLD) responses after dosing compared to before. Study participants demonstrating an increase (>50%) in post-contractile BOLD after tadalafil will be enrolled into Aim 2 of this study.
Cycling time to fatigue
Time frame: Baseline and 6 month follow-up visits of Aim 2.
The study will assess the impact of tadalafil on exercise performance and fatigue resistance compared to placebo. Participants will undergo a maximal effort cycling test before and after the intervention period. The time it takes for participants to reach exhaustion (TTE) will be recorded as the primary outcome measure. Measurement: Time to exhaustion (TTE) during a maximal effort cycling test on a recumbent, stationary ergometer. This test will quantify fatigue resistance by measuring the duration participants can sustain maximal effort cycling.
21 secondary outcomes
Quadriceps muscle Fat Fraction
Time frame: Aim 1 and Aim 2 (baseline and 6 month follow-up)
Metabolic recovery
Time frame: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Peak aerobic capacity (VO2max)
Time frame: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Minute Ventilation (VE)
Time frame: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Ventilatory Equivalent for Oxygen (VE/VO2)
Time frame: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Gas Exchange Threshold (GET)
Time frame: Through study completion, an average of 3 years.
cardiopulmonary exercise testing (CPET) - Workload at Anaerobic Threshold (W at AT)
Time frame: Through study completion, an average of 3 years.
The 100-meter timed test (100m)
Time frame: Through study completion, an average of 3 years.
the North Star Ambulatory Assessment (NSAA)
Time frame: Through study completion, an average of 3 years.
The 4-stair climb
Time frame: Through study completion, an average of 3 years.
The Physical activity questionnaire (PAQ-C)
Time frame: Through study completion, an average of 3 years.
Pulmonary function testing - vital capacity (FVC)
Time frame: Through study completion, an average of 3 years.
Pulmonary function testing - forced expiratory volume in 1 second (FEV1)
Time frame: Through study completion, an average of 3 years.
Neurology Quality of Life (NeuroQoL) pediatric lower extremity function
Time frame: Through study completion, an average of 3 years.
Patient Reported Outcomes Measurement Information System (PROMIS) pediatric fatigue
Time frame: Through study completion, an average of 3 years.
PROMIS parent proxy for physical activity
Time frame: Through study completion, an average of 3 years.
PROMIS pediatric physical activity
Time frame: Through study completion, an average of 3 years.
Physical Activity Monitoring - Daily Step Rate
Time frame: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in Low-Level Activity
Time frame: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in Moderate-Level Activity
Time frame: Through study completion, an average of 3 years.
Physical Activity Monitoring - Time in High-Level Activity
Time frame: Through study completion, an average of 3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Background: PubMed 34013753Lopez C, Taivassalo T, Berru MG, Saavedra A, Rasmussen HC, Batra A, Arora H, Roetzheim AM, Walter GA, Vandenborne K, Forbes SC. Postcontractile blood oxygenation level-dependent (BOLD) response in Duchenne muscular dystrophy. J Appl Physiol (1985). 2021 Jul 1;131(1):83-94. doi: 10.1152/japplphysiol.00634.2020. Epub 2021 May 20.
- Background: PubMed 32539076Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, Iammarino MA, Alfano LN, Nicholl A, Al-Zaidy S, Lewis S, Church K, Shell R, Cripe LH, Potter RA, Griffin DA, Pozsgai E, Dugar A, Hogan M, Rodino-Klapac LR. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. 2020 Sep 1;77(9):1122-1131. doi: 10.1001/jamaneurol.2020.1484.
- Background: PubMed 23277550Harper SQ. Molecular dissection of dystrophin identifies the docking site for nNOS. Proc Natl Acad Sci U S A. 2013 Jan 8;110(2):387-8. doi: 10.1073/pnas.1220256110. Epub 2012 Dec 31. No abstract available.
- Background: PubMed 30093306Duan D. Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy. Mol Ther. 2018 Oct 3;26(10):2337-2356. doi: 10.1016/j.ymthe.2018.07.011. Epub 2018 Jul 17.
- Background: PubMed 21695647Percival JM, Adamo CM, Beavo JA, Froehner SC. Evaluation of the therapeutic utility of phosphodiesterase 5A inhibition in the mdx mouse model of duchenne muscular dystrophy. Handb Exp Pharmacol. 2011;(204):323-44. doi: 10.1007/978-3-642-17969-3_14.
- Background: PubMed 24391598Thomas GD. Functional muscle ischemia in Duchenne and Becker muscular dystrophy. Front Physiol. 2013 Dec 18;4:381. doi: 10.3389/fphys.2013.00381.
- Background: PubMed 18953332Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, Campbell KP. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008 Nov 27;456(7221):511-5. doi: 10.1038/nature07414. Epub 2008 Oct 26.
- Background: PubMed 24330691Sheffield-Moore M, Wiktorowicz JE, Soman KV, Danesi CP, Kinsky MP, Dillon EL, Randolph KM, Casperson SL, Gore DC, Horstman AM, Lynch JP, Doucet BM, Mettler JA, Ryder JW, Ploutz-Snyder LL, Hsu JW, Jahoor F, Jennings K, White GR, McCammon SD, Durham WJ. Sildenafil increases muscle protein synthesis and reduces muscle fatigue. Clin Transl Sci. 2013 Dec;6(6):463-8. doi: 10.1111/cts.12121. Epub 2013 Oct 29.
- Background: PubMed 24808022Nelson MD, Rader F, Tang X, Tavyev J, Nelson SF, Miceli MC, Elashoff RM, Sweeney HL, Victor RG. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology. 2014 Jun 10;82(23):2085-91. doi: 10.1212/WNL.0000000000000498. Epub 2014 May 7.
- Background: PubMed 28972192Victor RG, Sweeney HL, Finkel R, McDonald CM, Byrne B, Eagle M, Goemans N, Vandenborne K, Dubrovsky AL, Topaloglu H, Miceli MC, Furlong P, Landry J, Elashoff R, Cox D; Tadalafil DMD Study Group. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology. 2017 Oct 24;89(17):1811-1820. doi: 10.1212/WNL.0000000000004570. Epub 2017 Sep 29.
- Background: PubMed 31375923Hoffman EP. Pharmacotherapy of Duchenne Muscular Dystrophy. Handb Exp Pharmacol. 2020;261:25-37. doi: 10.1007/164_2019_256.
- Background: PubMed 29067652Mah JK. An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy. Methods Mol Biol. 2018;1687:3-17. doi: 10.1007/978-1-4939-7374-3_1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tanja Taivassalo, Ph.D. principal investigator
University of Florida, College of Medicine, Department of Physiology and Aging
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tadalafil and Exercise Training in people with Duchenne Muscular Dystrophy and Duchenne Disease, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tanja Taivassalo, Ph.D. (352-294-8748, ttaivassalo@ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vascular responsiveness after muscle contraction to a single dose of tadalafil. (time frame: up to 4 weeks after the completion of Visits 1 and 2 of Aim 1.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06290713, which also lists 66 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.