Biomarker Development for Muscular Dystrophies

Current methods of measuring the response to new treatments for muscular dystrophies involve the examination of small pieces of muscle tissue called biopsies. The investigators are interested in finding less invasive methods that reduce the need for muscle biopsies. The purpose of this research is to learn about the possibility of detecting and measuring the activity and severity of muscular dystrophies by examining a urine sample and a blood sample, and some muscles in the arms and legs using tests called ultrasound and electrical impedance myography; both tests are painless and non-invasive. The information that is gathered from this study may help to evaluate, prevent, diagnose, treat, and improve the understanding of human muscle diseases.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Myotonic Dystrophy; Facioscapulohumeral Muscular Dystrophy

• Study Type: Observational
• Enrollment (Estimated): 465

Contacts and Locations

• Study Contact: Name: Tamkin Shahraki, MD; Phone Number: 617-726-7506; Email: tshahraki@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Anthony Amato, MD
      • Contact: Louis Beers; Email: lbeers@bwh.harvard.edu
    • Boston, Massachusetts, United States, 02129
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Tamkin Shahraki, MD; Phone Number: 617-726-7506; Email: tshahraki@mgh.harvard.edu
      • Principal Investigator: Thurman M. Wheeler, MD
      • Sub-Investigator: Paloma Gonzalez-Perez, MD, PhD
    • Boston, Massachusetts, United States, 02115
      • Active, not recruiting
      • Boston Children's Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest University
      • Contact: Constance Linville; Phone Number: 336-716-4568; Email: clinvill@wakehealth.edu
      • Principal Investigator: Araya Puwanant, MD
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh
      • Contact: Kerry M. Oddis, RN, CCRC; Phone Number: 412-692-4918; Email: kmoddis@upmc.edu
      • Principal Investigator: Paula R. Clemens, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Males and females ages 5 years and older with myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and facioscapulohumeral muscular dystrophy (FSHD) confirmed by genetic testing or by clinical history and examination are invited to participate. In addition, male and female healthy volunteers ages 18 and older also are invited to participate.

Description

Inclusion Criteria:

• Subjects with DM1 or DM2 based on genetic testing and/or clinical criteria (some subjects who have positive genetic testing may be asymptomatic, while other subjects who show characteristic clinical features may have declined to have genetic testing done). Control non-DM subjects are unknown to have DM or any other muscular dystrophy by history and may have had no genetic testing.
• Able to provide informed consent or assent for participation in the study.
• Demographic characteristics for single biofluid collection: Males and females age 5 years and older.
• Demographic characteristics for serial biofluid and muscle function testing: Males and females age 14 years and older with DM1.
• Demographic characteristics for biofluid and muscle biopsy: Males and females, ages 18-65 years.

Demographic characteristics for single biofluid collection, ultrasound, and myography: Males and females age 14 years and older.

Exclusion Criteria:

• Medical history of any of the following. State of immunosuppression; coagulopathy; pre-existing liver or kidney disease; documented HIV positive; documented hepatitis B and/or C positive.
• Medications and other drugs. Use of anti-platelet drugs within 7 days prior to blood draw or biopsy; use of anticoagulants within 60 days prior to blood draw or biopsy; active drug or alcohol use or dependence that, in the opinion of the biopsy surgeon, would interfere with post-procedure wound care.
• Other. Inability or unwillingness of the subject to give written informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Single biofluid collection; We will ask eligible volunteers to provide a single urine sample and undergo a single blood draw.
Serial biofluid and muscle function testing; We will ask eligible volunteers to provide a urine sample, a blood sample, and undergo standard muscle function tests once every six months over a two-year period, and undergo pulmonary function tests and electrocardiogram once per year for two years.
Biofluid and muscle tissue biopsy; We will ask eligible volunteers to provide a urine sample and undergo a muscle biopsy once.
Ultrasound and myography testing; We will ask eligible volunteers to provide a single urine sample, a single blood draw, and undergo ultrasound and electrical impedance myography studies once.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular RNA in biofluids	The extracellular RNA biomarkers in the muscular dystrophy groups will be evaluated and compared with the extracellular RNA content in control groups. Statistical analysis will be used to evaluate the sensitivity and specificity of these markers as measurements of disease activity and severity based on clinical measurements of muscle power, electrocardiogram parameters, pulmonary function test parameters, muscle tissue composition using quantitative ultrasound and electrical impedance myography, and muscle tissue specimens.	6 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: University of Pittsburgh; Boston Children's Hospital; Brigham and Women's Hospital; Wake Forest University
• Investigators: Principal Investigator: Thurman M. Wheeler, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Antoury L, Hu N, Balaj L, Das S, Georghiou S, Darras B, Clark T, Breakefield XO, Wheeler TM. Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies. Nat Commun. 2018 Sep 25;9(1):3906. doi: 10.1038/s41467-018-06206-0.
• Antoury L, Hu N, Darras B, Wheeler TM. Urine mRNA to identify a novel pseudoexon causing dystrophinopathy. Ann Clin Transl Neurol. 2019 May 17;6(6):1106-1112. doi: 10.1002/acn3.777. eCollection 2019 Jun.

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2015
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 4, 2023
• Last Verified: October 1, 2023

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; Neurodegenerative Diseases; Muscular Disorders, Atrophic; Heredodegenerative Disorders, Nervous System; Myotonic Disorders; Muscular Dystrophies; Muscular Dystrophy, Duchenne; Myotonic Dystrophy; Muscular Dystrophy, Facioscapulohumeral
• Other Study ID Numbers: 2014P001727

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