Clinical trial NCT02147639: Effects of Sodium Nitrate on Blood Flow in Becker Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Becker Muscular Dystrophy
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
First posted: 2014-05-28
Enrollment: 19
Sex: MALE
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Skeletal muscle blood flow
timeFrame: 24 hours after initial visit
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Heart Institute
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Ronald G Victor, MD
role: PRINCIPAL_INVESTIGATOR
References: