Extracellular RNA Biomarkers of Myotonic Dystrophy

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.

Study Overview

• Status: Recruiting
• Conditions: Myotonic Dystrophy

• Study Type: Observational
• Enrollment (Estimated): 215

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, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Hilda Gutierrez, MD; Email: hgutier1@bidmc.harvard.edu
      • Principal Investigator: Seward B. Rutkove, MD
      • Sub-Investigator: Courtney E. McIlduff, MD
      • Contact: Sarah Verga; Email: sverga@bidmc.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
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern
      • Contact: Karla Castro; Phone Number: 214-456-3696; Email: karla.castroochoa@utsouthwestern.edu
      • Principal Investigator: Susan T. Iannaccone, MD
      • Contact: Tammy Ramm; Phone Number: 214-867-5631; Email: tammy.ramm@utsouthwestern.edu

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) or myotonic dystrophy type 2 (DM2) 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 (DM1, DM2, and non-DM).
• Demographic characteristics for repeated measurements: Males and females age 14 years and older with DM1.
• Demographic characteristics for biofluid and muscle biopsy: Males and females, ages 18-65 years.

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. Women that are pregnant, or intend to become pregnant, prior to the biopsy; urine pregnancy test that is positive; inability or unwillingness of the subject to give written informed consent.
• Other. Inability or unwillingness of the subject to give written informed consent or assent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular RNA splice variants 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.	4 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Brigham and Women's Hospital; University of Texas
• 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): December 8, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 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): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Muscular Disorders, Atrophic; Muscular Dystrophies; Myotonic Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myotonic Dystrophy
• Other Study ID Numbers: 2020P000018

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