Effects of Sodium Nitrate on Blood Flow in Becker Muscular Dystrophy

This study is intended to build on a growing body of literature showing a blood flow abnormality in patients with Becker muscular dystrophy. The investigators' laboratory recently showed that this blood flow abnormality could be corrected by a single oral dose of the drug Tadalafil (also known as Cialis). The investigators now wish to replicate these exciting results using a common nitric oxide donor (sodium nitrate).

Study Overview

• Status: Completed
• Conditions: Becker Muscular Dystrophy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Sodium Nitrate; Dietary supplement: Sodium Nitrate - double dose; Procedure: Increased exercise intensity

Detailed Description

There are 2 phases to this research project: (1) an initial baseline study to confirm the blood flow abnormality in Becker muscular dystrophy, and (2) a subsequent brief treatment trial. There are also 3 optional study protocols: (A) dose-escalation trial, (B) placebo trial, and (C) increased exercise intensity trial.

The baseline study involves an intake history, physical examination, and phlebotomy for blood chemistries and DNA followed by non-invasive forearm blood flow studies (Near Infrared Spectroscopy, Doppler Ultrasound) before and after a brief bout of handgrip exercise (approximately 3-5 hours to complete). Blood flow studies will be performed with the subject's lower body enclosed in an airtight chamber. Blood flow and oxygen delivery to the forearm muscles will be measured before and during application of lower body negative pressure at rest and during handgrip exercise. Lower body negative pressure simulates the blood flow changes that normally occur when a person sits up after lying down.

The results of the baseline study will determine which patients meet preset eligibility criteria to participate in the medication phase of the study. These criteria include (1) normal kidney and liver function tests and normal BNP levels (the latter to exclude heart failure), and (2) abnormal blood flow responses to handgrip exercise.

Eligible patients will be asked to repeat the above laboratory procedures on a subsequent study day after receiving a single dose of sodium nitrate. Eligible patients will also be offered the option to repeat the above laboratory procedures on three subsequent study visits, where upon: (A) the dose of sodium nitrate is increased, (B) a placebo is ingested, and/or (C) the level of exercise in increased.

The investigators plan to enroll 20 adult men with Becker muscular dystrophy.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Heart Institute

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:

• Men 15-55 years of age with a pre-existing diagnosis of Becker Muscular Dystrophy by a clinical neurologist (based on clinical criteria plus previous muscle biopsy analysis and/or DNA analysis).

Exclusion Criteria:

• Any evidence of cardiopulmonary disease by history or by physical examination
• History of hypertension or blood pressure averaging ≥140/90 mmHg
• Diabetes mellitus or other systemic illness
• Heart failure by clinical exam, elevated BNP, or heart failure medication
• Serum creatinine ≥ 1.5 mg/dL
• Any history of substance abuse (including alcohol)
• Any history of psychiatric illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium Nitrate; Patients will ingest a single oral dose of sodium nitrate (~8.4 mmol)	Dietary supplement: Sodium Nitrate
No Intervention: Baseline; This is a baseline study visit, which will serve to assess inclusion and exclusion criteria, as well as provide untreated measurments of skeletal muscle blood flow and perfusion.
Experimental: Dose-escalation trial; This is an optional study visit, where subjects will ingest twice the dose of sodium nitrate (~16.8 mmol).	Dietary supplement: Sodium Nitrate - double dose
Placebo Comparator: Placebo-control trial; This is an optional study visit, where patients will ingest a placebo.	Dietary supplement: Placebo
Experimental: Increased exercise intensity; This is an optional study visit, where patients will be asked to repeat all of the blood flow assessments, but the exercise intensity will be increased.	Procedure: Increased exercise intensity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal muscle blood flow	Skeletal muscle blood flow regulation will be assessed at each visit by near infrared spectroscopy and Doppler ultrasound.	24 hours after initial visit

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 (Actual): October 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: March 25, 2014
• First Submitted That Met QC Criteria: May 22, 2014
• First Posted (Estimate): May 28, 2014

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: May 1, 2014

More Information

Terms related to this study

• 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: NANO3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No