What side effects are associated with this type of intervention?

Common treatments for Duchenne Muscular Dystrophy (DMD) include glucocorticoids and disease-modifying therapies like eteplirsen. Eteplirsen, a treatment aimed at increasing dystrophin production, has been shown to have no significant drug-related adverse effects in clinical trials. For treatments similar to Tadalafil, which is a PDE5 inhibitor, known side effects can include headache, flushing, dyspepsia, nasal congestion, back pain, and myalgia. These side effects are generally mild to moderate in severity.

What prior FDA approvals exist?

Eteplirsen is an FDA-approved drug for the treatment of Duchenne Muscular Dystrophy (DMD). It works by increasing dystrophin production in patients with specific dystrophin gene deletions. While Eteplirsen does not function through vasodilation or PDE5 inhibition like Tadalafil, it represents a significant advancement in DMD treatment. Tadalafil, a PDE5 inhibitor, is being studied for its potential to improve vascular responsiveness and slow disease progression in DMD by increasing blood flow to muscles.

What other types of research exist?

Promising alternatives to Tadalafil for Duchenne Muscular Dystrophy patients include Casimersen, which increases dystrophin production, and Ataluren, which promotes ribosomal read-through of nonsense mutations to produce functional proteins. Both treatments have shown efficacy in preliminary studies.

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Tadalafil for Duchenne Muscular Dystrophy

Q: What is the mechanism of action of this treatment?

The most common treatments for Duchenne Muscular Dystrophy (DMD) include casimersen, ataluren, and tadalafil. Casimersen increases dystrophin production through exon skipping, partially restoring the function of the dystrophin protein. Ataluren promotes ribosomal read-through of nonsense mutations, allowing the production of functional dystrophin protein. Tadalafil, a phosphodiesterase type 5 inhibitor, enhances vasodilation and increases blood flow, potentially countering muscle ischemia and improving muscle function. These treatments are crucial for DMD patients as they address the underlying genetic defects and improve muscle function, thereby slowing disease progression and enhancing quality of life.

Phase 2 & 3

Recruiting

Led By Tanja Taivassalo

Research Sponsored by University of Florida

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of DMD confirmed by 1) clinical history with features before the age of five, 2) physical examination, 3) elevated serum creatine kinase level and 4) absence of dystrophin expression, as determined by immunostaining or Western blot (<2%) and/or DNA confirmation of dystrophin mutation.

Minimum entry age of 7.0 years

Must not have

Older than 13.0 years of age

Presence of unstable medical problems

Timeline

Screening 3 weeks

Treatment Varies

Follow Up mri will be done 3 hours after dosing/no-dosing on two separate study visits

Awards & highlights

No Placebo-Only Group

Summary

This Trial will test if tadalafil can improve blood flow in the leg muscles of boys with DMD and see if it can help slow down the disease progression. Tadalafil is a medication that is approved for the treatment of certain conditions in men.

Who is the study for?

Boys aged 7 to 13 with Duchenne Muscular Dystrophy (DMD) confirmed by clinical history, physical exam, elevated creatine kinase levels, and lack of dystrophin protein. They must be able to walk and have no other conditions affecting muscle function or metabolism. Those with contraindications for MRI scans or taking certain medications like nitrates cannot participate.

What is being tested?

The trial is testing the effects of a single dose of Tadalafil, a drug that widens blood vessels, on leg muscle blood flow in boys with DMD using MRI or Doppler ultrasound after exercise. The goal is to see if this drug can improve blood flow and potentially slow disease progression.

What are the potential side effects?

Tadalafil may cause headaches, indigestion, back pain, muscle aches, flushing, stuffy or runny nose. These side effects usually go away after a few hours but can last longer in some cases.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with DMD based on my early symptoms, physical exams, high creatine kinase levels, and specific tests showing lack of dystrophin.

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I am at least 7 years old.

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I can walk on my own without help.

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I have been diagnosed with DMD based on my symptoms, tests, and genetic confirmation.

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I have been diagnosed with DMD based on my symptoms, tests, and genetic confirmation.

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I am at least 7 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am older than 13 years.

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I have medical conditions that are not well-controlled.

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I have a condition affecting my muscles, like myasthenia gravis.

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I am not taking nitrates, alpha-blockers, or other PDE5 inhibitors.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits

This trial's timeline: 3 weeks for screening, Varies for treatment, and doppler ultrasound will be done 3 hours after dosing/no-dosing on two separate study visits for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in post-contractile BOLD response after tadalafil dosing

Change in post-exercise hyperemia after tadalafil dosing

Secondary study objectives

Change in submaximal exercise capacity after tadalafil dosing

Side effects data

From 2017 Phase 4 trial • 635 Patients • NCT02224846

Viral upper respiratory tract infection

Periodontitis

Prostatitis

Alanine aminotransferase increased

Upper respiratory tract infection

Abdominal pain upper

Chronic gastritis

Blood uric acid increased

Insomnia

Enteritis

Rhinitis allergic

Sleep disorder

Rhinitis

Eczema

Pharyngitis

Influenza

Diabetes mellitus

Gout

Back pain

Gastritis

Urinary tract infection

Dizziness

Epistaxis

Renal cyst

Gastric polyps

Gastrooesophageal reflux disease

Nephrolithiasis

Hypertension

Pyrexia

Large intestine polyp

Abdominal distension

Abdominal pain

Dental caries

Diarrhoea

Gamma-glutamyltransferase increased

Headache

Cough

100%

80%

60%

40%

20%

Study treatment Arm

2.5 mg/5 mg Tadalafil

5 mg Tadalafil

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Tadalafil plus Doppler ultrasound (Schedule B)Experimental Treatment1 Intervention

The intervention is the same as in Schedule A; this arm will use Doppler ultrasound as the technique to monitor drug impact on skeletal muscle.

Group II: Tadalafil plus BOLD-MRI (Schedule A)Experimental Treatment1 Intervention

The intervention is the same as in Schedule B; this arm will use BOLD-MRI as the technique to monitor drug impact on skeletal muscle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tadalafil

2014

Completed Phase 4

~3280

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Duchenne Muscular Dystrophy (DMD) include casimersen, ataluren, and tadalafil. Casimersen increases dystrophin production through exon skipping, partially restoring the function of the dystrophin protein. Ataluren promotes ribosomal read-through of nonsense mutations, allowing the production of functional dystrophin protein. Tadalafil, a phosphodiesterase type 5 inhibitor, enhances vasodilation and increases blood flow, potentially countering muscle ischemia and improving muscle function. These treatments are crucial for DMD patients as they address the underlying genetic defects and improve muscle function, thereby slowing disease progression and enhancing quality of life.

Ameliorative Effect of Phosphodiesterase-5 Inhibitor in Rat Model of Vascular Dementia.PDE5 inhibitors: considerations for preference and long-term adherence.Tadalafil for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.