Sodium Nitrate for Muscular Dystrophy

Study Overview
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Brief Summary
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The investigators' previous work in males with Becker Muscular Dystrophy shows that functional sympatholysis is restored by acute inorganic nitrate supplementation. This was translated from work using the mdx mouse model of dystrophinopathy. Recent work has shown that there is a frank improvement in grip strength when mdx mice are treated with an inorganic Nitric Oxide (NO) donor. The purpose of this study is to determine if chronic treatment with an inorganic NO donor can benefit patients with muscular dystrophy beyond blood flow regulation.

Official Title
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Sodium Nitrate for Muscular Dystrophy

Conditions
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Becker Muscular Dystrophy

Intervention / Treatment
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* Drug: Sodium Nitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of muscular dystrophy Age 15-45 years of age Ambulatory No clinical evidence of heart failure Maximum voluntary contraction, measured by hand grip dynamometer, of 20-40 kg Exclusion Criteria: Hypertension, diabetes, or heart failure by standard clinical criteria Elevated B-type Natruiretic Peptide level (>100 pg/ml) Left Ventricular Ejection Fraction < 50% Wheelchair bound Cardiac rhythm disorder, specifically: rhythm other than sinus, Supraventricular Tachycardia, atrial fibrillation, ventricular tachycardia Continuous ventilatory support Liver disease Renal impairment Contraindications to NO donors (use of nitrates, alpha-blockers, CYP3A inhibitors, amlodipine, or Phosphodiesterase type 5 (PDE5) inhibitors) Glucocorticoid therapy and prophylactic use of Angiotensin Converting Enzyme (ACE) inhibitors and beta-blockers for cardiac protection will not be exclusion criteria. Maximum voluntary contraction of less than 20 kg or greater than 40 kg Ventilation Devices (Continuous Positive Airway Pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP))

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium Nitrate (Beetroot Juice)<br>Sodium nitrate in the form of beetroot juice will be administered orally. Patients will be assessed with a number of functional muscle assessments. | Drug: Sodium Nitrate<br>* Patients will be given sodium nitrate daily in the form of beetroot juice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximal handgrip strength |  | Change from baseline in handgrip strength at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle function - Performance of Upper Limb Scale | Change in functional muscle assessment as measured by the Performance of Upper Limb Scale | Change from baseline in muscle function - the Performance of Upper Limb Scale at 3 months | 
| Change in muscle tissue markers - histology and proteomics | Change in tissue markers such as neuronal Nitric Oxide Synthase (nNOS) content and location and nitrosative stress by histology and proteomics | Change from baseline in muscle tissue markers at 3 monthss | 
| Change in systolic wall strain - imaging | Change in the cardiac wall strain as measured by Cardiac Magnetic Resonance Imaging | Change from baseline in cardiac systolic wall strain at 3 months | 
| Change in muscle function - North Star Ambulatory Assessment | Change in functional muscle assessment as measured by the North Star Ambulatory Assessment | Change from baseline in muscle function - North Star Ambulatory Assessment at 3 months | 
| Change in muscle function - 6 minute walk test | Change in functional muscle assessment as measured by the 6 minute walk test | Change from baseline in muscle function - 6 minute walk test at 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Becker, Dystrophy