Magnetic Resonance and Optical Imaging of Dystrophic and Damaged Muscle

Optical Imaging of Dystrophic and Damaged Muscle

The purpose of this research study is to determine the potential of Optical Imaging techniques to detect muscle damage in boys with Duchenne Muscular Dystrophy and unaffected exercised muscle. Healthy subjects will undergo two different exercises in opposite forearms before any imaging techniques are performed. Boys with Duchenne Muscular Dystrophy will only undergo the imaging techniques without exercise.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Procedure: Optical and Magnetic Resonance Imaging and Spectroscopy; Other: Exercising

Detailed Description

The overall objective of this proposal is to validate the potential of Optical Imaging techniques to be able to detect and quantify muscle damage in a population affected by Duchenne Muscular Dystrophy, a muscle wasting disease, and in a healthy population that has undergone temporal muscle damage resulting from an exercising intervention.

Duchenne Muscular Dystrophy is a relentlessly progressive degenerative muscle wasting disease, clinically characterized by progressive muscle weakness, a loss of ambulation, and premature mortality. Currently, no known cure exists and treatments that benefit patients diagnosed with Duchenne Muscular Dystrophy are limited. New approaches, such as cell therapy, gene transfer, and pharmacological interventions have shown promising results in animal models and human studies with great potential to develop as effective therapeutic treatments. One of the major limitations of testing these interventions; however. is the lack of effective methods to monitor cellular and tissue changes taking place in the response to therapy. The ability to determine cellular and tissue specific changes in damaged muscles in real time, non-invasively, repeatedly, without exposure to any harmful radiations, with minimal patient discomfort, and at low operating cost would enable high throughput and faster investigation of potential therapies.

The proposed study focuses on the development of Optical Imaging technologies in the near infrared range of wavelengths to differentiate damaged from normal muscle tissue. Near infrared light (700 - 900 nm) has demonstrated the ability to deeply penetrate through biological tissue, skin, and muscle without appreciable attenuation or auto-fluorescence.

The investigators anticipate that Indocyanine Green enhanced Optical Imaging can be used to image exercise induced acute muscle damage in healthy individuals and damaged muscle and in boys with Duchenne Muscular Dystrophy. It is anticipated that this work may fulfill the need for imaging biomarkers that monitor and quantify cellular damage, muscle perfusion, and drug delivery - non-invasively, using benign light, repeatedly, and in real time, with the intention of accelerating the testing of efficacy in clinical trials for neuromuscular disorders. The study is designed to determine the ability of Optical Imaging as a reliable, safe, relatively inexpensive, and facile tool to detect and quantify muscle damage. Investigators anticipate that this type of imaging modality will provide clinically useful information for diagnostic and prognostic purposes in patients with neuromuscular diseases, especially boys with Duchenne Muscular Dystrophy.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 55 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria for Duchenne Muscular Dystrophy subjects:

• Diagnosis of Duchenne muscular dystrophy confirmed by 1) clinical history with features before the age of 5 years, 2) physical examination, 3) elevated serum creatine kinase level, and 4) absence of dystrophin expression as determined by immune stain or Wester blot (<2%) and/or DNA confirmation of dystrophin mutation
• Must be between 10-15 years of age.
• Must be male.

Inclusion Criteria for unaffected subjects:

• Must be older than 18 years of age.
• Must be male.

Exclusion Criteria for unaffected and Duchenne Muscular Dystrophy subjects:

• Contraindication to an Magnetic Resonance examination (e.g. aneurysm clip, severe claustrophobia, magnetic implants)
• Presence of a condition in patients that impacts muscle function or muscle metabolism (e.g. myasthenia gravis, endocrine disorder, mitochondrial disease)
• Medical condition leading to developmental delay or impaired motor control (e.g. cerebral palsy)
• Unstable medical condition (e.g. uncontrolled seizure disorder)
• Behavioral problems causing an inability to cooperate during testing
• Control subjects who are participating in sport specific training 2 times or more per week
• History of allergy to iodides

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Duchenne Muscular Dystrophy; This arm will only include subjects that have a confirmed diagnosis of Duchenne Muscular Dystrophy. Subjects in this arm will not undergo any exercising, and will only be imaged by Optical and Magnetic Resonance Imaging and Spectroscopy techniques at a single time point.	Procedure: Optical and Magnetic Resonance Imaging and Spectroscopy; This arm will contain subjects that are not affected by Duchenne Muscular Dystrophy. These subjects will undergo concentric exercising of one forearm, and eccentric exercising of the contralateral forearm. Two days following the exercising, subjects will undergo Optical Imaging and Magnetic Resonance Imaging and Spectroscopy.
EXPERIMENTAL: Non-affected Subjects; This arm will contain subjects that are not affected by Duchenne Muscular Dystrophy. These subjects will undergo concentric exercising of one forearm, and eccentric exercising of the contralateral forearm. Two days following the exercising, subjects will undergo Optical Imaging and Magnetic Resonance Imaging and Spectroscopy.	Procedure: Optical and Magnetic Resonance Imaging and Spectroscopy; This arm will contain subjects that are not affected by Duchenne Muscular Dystrophy. These subjects will undergo concentric exercising of one forearm, and eccentric exercising of the contralateral forearm. Two days following the exercising, subjects will undergo Optical Imaging and Magnetic Resonance Imaging and Spectroscopy.; Other: Exercising; This arm will only include subjects that have a confirmed diagnosis of Duchenne Muscular Dystrophy. Subjects in this arm will not undergo any exercising, and will only be imaged by Optical and Magnetic Resonance Imaging and Spectroscopy techniques at a single time point.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indocyanine Green accumulation in forearm muscles	Percentage of area with elevated Indocyanine Green in muscle will be an indicator of cell membrane damage and will be measured using Optical Imaging in the forearms of study participants.	Up to 2 days
Muscle T2 elevation in forearm muscles	Muscle T2 is a noninvasive marker of muscle damage/inflammation and will be measured using Magnetic Resonance in the forearms of participants of this study.	Up to 2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed Onset of Muscle Soreness (DOMS)	DOMS will be correlated to percentage of elevated pixels within forearms of study participants.	Up to 2 days
Serum Creatine Kinase	Serum Creatine Kinase is a marker of muscle damage and will be correlated to percentage of elevated pixels within forearms of study participants	Up to 2 days

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Glenn A Walter, Ph.D., University of Florida

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (ACTUAL): January 8, 2018
• Study Completion (ACTUAL): January 8, 2018

Study Registration Dates

• First Submitted: June 6, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (ESTIMATE): June 20, 2014

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Exercise; Optical Imaging; Duchenne Muscular Dystrophy; Magnetic Resonance
• 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: IRB201602354; MD110050 (OTHER: Department of Defense); 536-2012 (OTHER: UF legacy study)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No