Sodium Nitrate for Muscular Dystrophy

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.

Study Overview

• Status: Completed
• Conditions: Becker Muscular Dystrophy
• Intervention / Treatment: Drug: Sodium Nitrate

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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))

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Nitrate (Beetroot Juice); 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; Patients will be given sodium nitrate daily in the form of beetroot juice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Ronald G Victor, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Becker; Dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: Pro35228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No