Tadalafil + Exercise for Duchenne Muscular Dystrophy

Overseen By Ruby Sullivan, MS

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Florida

Must be taking: Glucocorticoids

Must not be taking: Nitrates, Alpha-blockers

Disqualifiers: Severe cardiomyopathy, Uncontrolled seizures, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 26 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two potential treatments for Duchenne muscular dystrophy (DMD) to improve muscle function and vascular health. It combines aerobic exercise training with tadalafil, a drug that improves blood flow. Participants are divided into two groups: one taking tadalafil and the other receiving a placebo, both alongside exercise. This trial targets individuals who can walk, have been diagnosed with DMD through genetic testing, and are on a stable glucocorticoid treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable glucocorticoid regimen for more than 3 months. You cannot take certain medications like nitrates, alpha-adrenergic blockers, or other drugs that affect blood flow or muscle metabolism.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tadalafil is generally safe. Studies have found no harmful effects on heart function in those using tadalafil. Tests such as heart ultrasounds and ECGs revealed no negative changes. The FDA has approved tadalafil for other uses, indicating it is well-tolerated. Although some studies found it didn't slow walking decline in boys with Duchenne muscular dystrophy, this relates more to its effectiveness than its safety. Overall, tadalafil appears to be a safe choice for those considering joining a trial that includes it. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for Duchenne muscular dystrophy?

Unlike the standard treatments for Duchenne Muscular Dystrophy, which often focus on corticosteroids to manage symptoms, tadalafil offers a novel approach by targeting blood flow. Tadalafil, more commonly known as a treatment for erectile dysfunction, may help improve muscle function in Duchenne patients by enhancing blood flow to muscles during exercise. Researchers are excited about this treatment because it could complement existing therapies, potentially offering a new way to preserve muscle strength and function. This combination of tadalafil with exercise might provide a synergistic effect, offering hope for better management of the condition.

What evidence suggests that this trial's treatments could be effective for Duchenne muscular dystrophy?

This trial will compare Tadalafil with a placebo, both combined with exercise, for treating Duchenne muscular dystrophy (DMD). Research has shown mixed results for tadalafil in treating DMD. Some studies indicate it does not slow the loss of walking ability in boys with DMD. However, evidence suggests tadalafil might improve blood flow in muscles, potentially aiding muscle function. No negative effects on heart health have been reported, so it is considered safe for the heart. While more research is needed, tadalafil's impact on blood flow offers hope for improving muscle health in DMD. ^{1 2 3 5 6}

Who Is on the Research Team?

Tanja Taivassalo, Ph.D.

Principal Investigator

University of Florida, College of Medicine, Department of Physiology and Aging

Are You a Good Fit for This Trial?

This trial is for boys diagnosed with Duchenne muscular dystrophy (DMD), confirmed by a genetic report, who are at least 6 years old and can walk. They must be on a stable glucocorticoid regimen for over three months.

Inclusion Criteria

My diagnosis of Duchenne Muscular Dystrophy is confirmed by a genetic report.

I am at least 6 years old.

I can walk on my own without help.

Exclusion Criteria

Contraindication to a Magnetic resonance Imaging examination (e.g. severe claustrophobia, magnetic implants, unable/unwilling to perform test)

I have a condition like cerebral palsy or a history of muscle breakdown without cause.

Participation in currently approved FDA trials or other investigational clinical trials during the period of the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Drug Responsiveness Testing

Testing for drug responsiveness after a single dose of tadalafil to assess increase in muscle oxygenation

up to 4 weeks

2 visits (in-person)

Treatment

Participants receive daily tadalafil or placebo combined with structured cycle exercise training for 6 months

26 weeks

Regular virtual monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tadalafil

Trial Overview The study tests the effects of tadalafil, a vasodilator that improves blood flow, combined with aerobic exercise training to see if they improve muscle function and cardiovascular health in DMD patients.

How Is the Trial Designed?

Group I: Tadalafil and Exercise Arm Experimental Treatment 2 Interventions

Participants receive tadalafil weight-dependent dosage to take daily for 6 months (26 weeks).

Group II: Placebo and Exercise Arm Placebo Group 2 Interventions

Participants receive a tadalafil placebo tablet matching the tadalafil weight-dependent dosage to take daily for 6 months (26 weeks).

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

Tadalafil, a new oral treatment for erectile dysfunction, is highly effective with a duration of action lasting up to 36 hours, making it a convenient option for patients.

The medication has a strong safety profile, with only a few mild to moderate side effects reported, which is particularly important for patients who may have other medical conditions or take multiple medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tadalafil for erectile dysfunction: excellent safety and tolerance]. Bai, WJ.[2015]

Chronic treatment with the PDE5 inhibitor tadalafil in mdx mice showed significant improvements in skeletal muscle function, indicating its potential as a therapeutic approach for Duchenne and Becker Muscular Dystrophy.

Tadalafil treatment led to multiple beneficial effects, including enhanced lipid metabolism, a shift towards slow oxidative muscle fibers, improved protein synthesis efficiency, and better organization of the actin network, suggesting a multifaceted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathways Implicated in Tadalafil Amelioration of Duchenne Muscular Dystrophy. De Arcangelis, V., Strimpakos, G., Gabanella, F., et al.[2016]

In a study involving 12 healthy male volunteers with high cardiorespiratory fitness, a single dose of tadalafil (20 mg) led to increased levels of muscle damage markers, specifically creatine kinase (CK) and lactate dehydrogenase (LDH), 24 hours after ingestion.

Despite the increase in muscle damage markers, tadalafil did not affect redox homeostasis or antioxidant enzyme activities, suggesting that while it may have some effects on muscle damage, it does not enhance antioxidant status in fit individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Tadalafil Administration on Redox Homeostasis and Polyamine Levels in Healthy Men with High Level of Physical Activity. Duranti, G., Ceci, R., Di Luigi, L., et al.[2021]

In a randomized, double-blind, placebo-controlled trial involving adults with Duchenne and Becker muscular dystrophies (DBMD) and cardiomyopathy, sildenafil did not show significant improvement in cardiac function compared to placebo, as indicated by no statistically significant differences in left ventricular end-systolic volume after 6 months.

The study was terminated early due to a higher number of subjects worsening on sildenafil, suggesting that this treatment may not be beneficial for improving cardiac health in DBMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Leung, DG., Herzka, DA., Thompson, WR., et al.[2022]

Tadalafil, a phosphodiesterase type 5 inhibitor, has shown promise in preventing cardiomyopathy in models of Duchenne muscular dystrophy, including mdx mice and golden retriever muscular dystrophy dogs, by blunting the adrenergic response and promoting cardioprotective signaling.

In golden retriever muscular dystrophy dogs treated with tadalafil before the onset of cardiomyopathy, cardiac function was preserved and histopathological improvements were observed, suggesting that tadalafil could be an effective therapy to delay cardiomyopathy in Duchenne muscular dystrophy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tadalafil Treatment Delays the Onset of Cardiomyopathy in Dystrophin-Deficient Hearts. Hammers, DW., Sleeper, MM., Forbes, SC., et al.[2023]

In a randomized trial involving 331 boys aged 7 to 14 with Duchenne muscular dystrophy (DMD), tadalafil did not significantly reduce the decline in walking ability over 48 weeks, as measured by the 6-minute walk distance (6MWD).

While tadalafil showed no overall effect on primary and secondary outcomes, it did suggest a potential benefit in upper limb function for boys over 10 years old, indicating that earlier initiation of treatment might be worth exploring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Victor, RG., Sweeney, HL., Finkel, R., et al.[2022]

Tadalafil is generally safe and well-tolerated for chronic treatment of erectile dysfunction, even in high-risk populations, with most side effects being mild or moderate and reversible without stopping the medication.

It does not increase the risk of cardiovascular issues and can be safely used alongside antihypertensive medications and selective alpha-receptor blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and tolerance of tadalafil in the treatment of erectile dysfunction]. He, XY.[2015]

In a study of 23 subjects with stable coronary artery disease (CAD), tadalafil did not significantly change the time to exercise-induced myocardial ischaemia compared to a placebo, indicating it may not improve exercise tolerance in these patients.

Tadalafil was associated with a notable reduction in resting and exercise-induced systolic blood pressure, which raises safety concerns about its use alongside nitrates due to the risk of hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of tadalafil on the time to exercise-induced myocardial ischaemia in subjects with coronary artery disease. Patterson, D., Kloner, R., Effron, M., et al.[2018]

In a phase 3 trial involving 82 boys with Duchenne muscular dystrophy, tamoxifen was found to be safe and well tolerated, with no significant difference in motor function improvement compared to placebo after 48 weeks.

Although there were indications of slower disease progression in the tamoxifen group, the differences were not clinically or statistically significant, leading to the conclusion that tamoxifen cannot be recommended as a treatment option for Duchenne muscular dystrophy at this time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy (TAMDMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Henzi, BC., Schmidt, S., Nagy, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28972192/

A phase 3 randomized placebo-controlled trial of tadalafil for ... Results: Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5664308/

A phase 3 randomized placebo-controlled trial of tadalafil ... This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01865084

A Study of Tadalafil for Duchenne Muscular Dystrophy The main purpose of this study is to determine if tadalafil can slow the decline in walking ability of boys who have Duchenne muscular dystrophy (DMD).

4. neurologylive.com neurologylive.com/view/tadalafil-improves-microvascular-function-duchenne-leg-muscles

Tadalafil Improves Microvascular Function in Duchenne ... Results showed an increase in BOLD response after treatment, from 1.9% (SD, 1.6%) to 3.2% (SD, 0.8%) in DMD (P = .09), while the BOLD-response ...

5. bmccardiovascdisord.biomedcentral.com bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-025-04727-3

Effect of Tadalafil on cardiac function and left ventricular ... No adverse effects of tadalafil on cardiovascular function were evident based on adverse events, echocardiograms, ECG, or vital sign measurements through 48 ...

6. fda.gov fda.gov/media/112224/download

Clinical Review Rainer W. Paine, MD, PhD NDA ... It showed that there is no benefit in the treatment with tadalafil of patients with DMD. 6.1.15. Safety Results. The applicant reports that of ...