The Study of Skeletal Muscle Blood Flow in Becker Muscular Dystrophy

Skeletal Muscle Blood Flow in Becker Muscular Dystrophy

This pilot study tests the hypothesis that the medication nitric oxide extract from beetroot juice improves blood flow to the skeletal muscle during exercise. The investigators will use cutting edge technology with contrast enhanced ultrasound to visualize the microvascular blood supply to the forearm. Animal studies have shown reversal of muscle damage with improved delivery of blood to the exercising muscle. This research aims to understand the mechanism of action of this medication in a way it has never been studied before. The results may help benefit individuals with muscular Dystrophy in the future.

Study Overview

• Status: Terminated
• Conditions: Muscular Dystrophy
• Intervention / Treatment: Drug: Tadalafil 20 MG; Other: beetroot juice extract

Detailed Description

The subjects are asked to perform a graded hand-grip exercise while blood flow to the skeletal muscle is visualized by contrast enhanced ultrasound.

This is done at baseline and after taking the study agent.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Early 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: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy man, aged 18 to 45 years, currently taking no medication. OR
• Clinical diagnosis of Becker Muscular Dystrophy (BMD), aged 18 to 45 years, and currently taking no medication.

Exclusion Criteria:

• Hypertension, diabetes, heart failure, liver disease
• ECG evidence of prolonged QT interval

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls (HC); Healthy men currently taking no medications will be asked to perform graded hand-grip exercise while a contrast enhanced ultrasound (CEU) probe is placed over their forearm to measure blood flow. This is repeated at baseline and shortly after taking beetroot juice extract.	Drug: Tadalafil 20 MG; Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.; Other: beetroot juice extract; Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.
Experimental: Becker Muscular Dystrophy (BMD); currently taking no medications will be asked to perform graded hand-grip exercise while a contrast enhanced ultrasound (CEU) probe is placed over their forearm to measure blood flow. Using a lower body negative pressure (LBNP) chamber, the subjects are tested for impaired exercise induced vasodilation to the skeletal muscle or "functional sympatholysis". This is repeated at baseline and shortly after taking beetroot juice extract.	Drug: Tadalafil 20 MG; Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.; Other: beetroot juice extract; Blood flow to the forearm is visualized via an ultrasound technique at rest and with graded exercise. The experiment is then repeated shortly after the subject takes the study agent, beetroot juice extract.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Skeletal Muscle Blood Flow	Exercise induced skeletal muscle perfusion is measured by contrast-enhanced ultrasound (CEU) during graded voluntary contraction on a hand grip dynamometer.	At baseline and within one hours after taking beetroot juice or Tadalafil

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Measured Functional Sympatholysis	Functional sympatholysis (attenuation of exercise induced skeletal muscle vasoconstriction) is assessed using a lower body negative pressure chamber.	At baseline, and within an hour after taking beetroot juice or Tadalafil
Change in Measured Flow Mediated Dilation (FMD)	Endothelial function is assessed by measuring flow-mediated dilation (FMD) by Doppler ultrasound.	At baseline, and within an hour after taking beetroot juice or Tadalafil

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): November 1, 2017
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: January 10, 2016
• First Posted (Estimate): January 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 14, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Ultrasound; Muscular Dystrophy; blood flow; Becker; Skeletal Muscle
• 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; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: Pro00041688

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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