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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sodium Nitrate | Experimental | Patients will ingest a single oral dose of sodium nitrate (~8.4 mmol) |
|
| Baseline | No Intervention | 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. | |
| Dose-escalation trial | Experimental | This is an optional study visit, where subjects will ingest twice the dose of sodium nitrate (~16.8 mmol). |
|
| Placebo-control trial | Placebo Comparator | This is an optional study visit, where patients will ingest a placebo. |
|
| Increased exercise intensity | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sodium Nitrate | Dietary Supplement |
| ||
| Sodium Nitrate - double dose |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ronald G Victor, MD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Heart Institute | Los Angeles | California | 90048 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41671094 | Derived | Mickle AT, Johnston KM, Ricchetti-Masterson KL, Kennedy AR, Korpach SG, Gooch KL. The natural history of Becker muscular dystrophy: A systematic literature review. J Neuromuscul Dis. 2026 Feb 1:22143602261420045. doi: 10.1177/22143602261420045. Online ahead of print. |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C031618 | sodium nitrate |
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| Dietary Supplement |
|
| Placebo | Dietary Supplement |
|
| Increased exercise intensity | Procedure |
|
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |