The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy

Study Overview
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Brief Summary
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This pilot study tests the hypothesis that the medication nitric oxide extract from beetroot juice improves blood flow to the skeletal muscle during exercise. The investigators will use cutting edge technology with contrast enhanced ultrasound to visualize the microvascular blood supply to the forearm. Animal studies have shown reversal of muscle damage with improved delivery of blood to the exercising muscle. This research aims to understand the mechanism of action of this medication in a way it has never been studied before. The results may help benefit individuals with muscular Dystrophy in the future.

Detailed Description
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The subjects are asked to perform a graded hand-grip exercise while blood flow to the skeletal muscle is visualized by contrast enhanced ultrasound. This is done at baseline and after taking the study agent.

Official Title
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Skeletal Muscle Blood Flow in Becker Muscular Dystrophy

Conditions
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Muscular Dystrophy

Intervention / Treatment
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* Drug: Tadalafil 20 MG
* Other: beetroot juice extract


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy man, aged 18 to 45 years, currently taking no medication. OR Clinical diagnosis of Becker Muscular Dystrophy (BMD), aged 18 to 45 years, and currently taking no medication. Exclusion Criteria: Hypertension, diabetes, heart failure, liver disease ECG evidence of prolonged QT interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Controls (HC)<br>Healthy men currently taking no medications will be asked to perform graded hand-grip exercise while a contrast enhanced ultrasound (CEU) probe is placed over their forearm to measure blood flow. This is repeated at baseline and shortly after taking beetroot juice extract. | Drug: Tadalafil 20 MG<br>* Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.<br>Other: beetroot juice extract<br>* Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.<br>|
| Experimental: Becker Muscular Dystrophy (BMD)<br>currently taking no medications will be asked to perform graded hand-grip exercise while a contrast enhanced ultrasound (CEU) probe is placed over their forearm to measure blood flow. Using a lower body negative pressure (LBNP) chamber, the subjects are tested for impaired exercise induced vasodilation to the skeletal muscle or functional sympatholysis. This is repeated at baseline and shortly after taking beetroot juice extract. | Drug: Tadalafil 20 MG<br>* Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.<br>Other: beetroot juice extract<br>* Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Skeletal Muscle Blood Flow | Exercise induced skeletal muscle perfusion is measured by contrast-enhanced ultrasound (CEU) during graded voluntary contraction on a hand grip dynamometer. | At baseline and within one hours after taking beetroot juice or Tadalafil | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Measured Functional Sympatholysis | Functional sympatholysis (attenuation of exercise induced skeletal muscle vasoconstriction) is assessed using a lower body negative pressure chamber. | At baseline, and within an hour after taking beetroot juice or Tadalafil | 
| Change in Measured Flow Mediated Dilation (FMD) | Endothelial function is assessed by measuring flow-mediated dilation (FMD) by Doppler ultrasound. | At baseline, and within an hour after taking beetroot juice or Tadalafil | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Becker, Muscular Dystrophy, Skeletal Muscle, blood flow, Ultrasound