Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1) Extension

NCT07700225 | Recruiting

• 1 other identifier: HM300000528 END-EXT
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder that causes progressive disability and shortened life expectancy. It is characterized by progressive weakness and myotonia, which preferentially affects the craniofacial, hand, and distal leg muscles. Many patients also experience difficulties with cognition, cardiac arrhythmias, respiratory failure, or cataracts. Currently there is no treatment to slow progression or reverse the symptoms.

Conditions

DM1; Myotonic Dystrophy; Myotonic Dystrophy 1; Myotonic Dystrophy Type 1; Myotonic Dystrophy Type-1; Myotonic Dystrophy, Type 1 (DM1); Myotonic Muscular Dystrophy

Keywords

DM1; END-EXT; END-DM1 Extension; Myotonic Dystrophy Type 1; Steinert's Disease; Muscular Dystrophy; Neuromuscular Disease; DMPK; Natural History; Myotonia; DMCRN; Myotonic Dystrophy Clinical Research Network

Outcome Measures

Primary Outcomes (6)

• Characterize the long-term disease progression- 10 meter walk/run

  The 10-meter walk test (10MWT) is used in research to reliably measure gait speed, assessing functional mobility and detecting changes in walking performance over time. It is a highly reliable, quick, and cost-effective tool. . It is favored for its simplicity, speed, and ability to predict functional independence. A "good" score varies by age/condition, with healthy adults averaging over 1.2-1.4 m/s.

  Baseline (0 months), every 12 months over four years

• Characterize the long-term disease progression- vHOT

  The Video Hand Opening Time (vHOT) is used in research as a practical, low-cost, and reliable quantitative tool to measure handgrip myotonia (delayed muscle relaxation) in Myotonic Dystrophy Type 1 (DM1) patients. It is particularly valuable for multicenter clinical trials because it allows for blinded, objective assessment of therapeutic responses. A "good" (healthy) score is generally as close to zero as possible.

  Baseline (0 months), every 12 months over four years

• Characterize the long-term disease progression- grip strength

  Grip strength is used in research as a reliable, low-cost biomarker for overall muscle strength, aging, and mortality risk. A good score varies by age and sex, with healthy young adults often averaging over 40-45 kg (males) and 25-30kg (females).

  Baseline (0 months), every 12 months over four years

• Characterize the long-term disease progression- ECG

  Electrocardiograms (ECGs/EKGs) are used in research for their non-invasive, cost-effective ability to track heart rhythm, diagnose cardiac conditions, and assess cardiovascular disease risk. In research, a "good" ECG score indicates normal sinus rhythm and intervals, such as a PR interval of 120-200 milliseconds and an RR interval of 0.6-1.2 seconds.

  Baseline (0 months), every 12 months over four years

• Characterize the long-term disease progression- FVC

  Forced Vital Capacity (FVC) is crucial in research for diagnosing and tracking restrictive lung diseases (e.g., pulmonary fibrosis), assessing disease progression, and measuring treatment efficacy in clinical trials. A "good" or normal FVC is typically 80% or higher of the predicted value, based on a patient's age, height, sex, and ethnicity.

  Baseline (0 months), every 12 months over four years

• Characterize the long-term disease progression- DM1-Activ-c

  The DM1-Activ-c (25-item) is a validated, Rasch-built, patient-reported outcome measure designed specifically to assess daily activity and participation in Myotonic Dystrophy Type 1 (DM1) patients. It is used in research for its high sensitivity to disease progression and therapeutic changes (responsiveness), making it a reliable primary endpoint for clinical trials to measure patient improvement. The DM1-Activ-c is scored on a scale from 0 to 100, where higher scores indicate better functional ability.

  Baseline (0 months), every 12 months over four years

Study Arms (1)

Myotonic Dystrophy Type 1 (DM1) Longitudinal Cohort

Participants with a clinical or genetic diagnosis of myotonic dystrophy type 1 (DM1) or congenital myotonic dystrophy (CDM). This cohort includes individuals transitioning from the parent study, Establishing Biomarkers and Clinical Endpoints in Myotonic Dystrophy Type 1 (END-DM1; NCT03981575), as well as newly enrolled participants.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study seeks to enroll at least 1000 men and women aged 18 to 70 with a positive genetic test for myotonic dystrophy type 1, a clinical diagnosis of myotonic dystrophy type 1, or a clinical diagnosis or positive genetic test for congenital myotonic dystrophy. based on research criteria. Few restrictions are placed on participation in the study because we aim to capture the full spectrum of disease severity.

You may qualify if:

• Age 18 to 70 years (inclusive)
• Clinical diagnosis of DM1 based on research criteria or positive genetic test. The research criteria for clinical diagnosis of DM1 require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in \> 99% of individuals who satisfied these criteria. OR A diagnosis of CDM, which is defined as children having symptoms of myotonic dystrophy in the newborn period (\<30 days), such as hypotonia, feeding or respiratory difficulty, requiring hospitalization to a ward or to the neonatal intensive care unit for 3 days or more; and a genetic test suspicious of an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or first degree relative. An expanded CTG repeat size in the child is considered greater than 200 repeats or E1-E4 classification (E1= 200-500, E2=500-1,000, E3=1,000-1,500, E4\>1,500)

You may not qualify if:

• Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than in situ skin cancer.
• Current alcohol or substance use disorder.
• Concurrent pregnancy or planned pregnancy during the course of the study.
• Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator. compromise performance on study measures.
• Use of mexiletine or other anti-myotonia agents within 72 hours of any study visit.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• Dyne Therapeutics: collaborator
• Myotonic Dystrophy Clinical Research Network (DMCRN): collaborator
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

Related Publications (12)

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  PMID: 8835099 BACKGROUND

• Griggs RC, Wood DS. Criteria for establishing the validity of genetic recombination in myotonic dystrophy. Neurology. 1989 Mar;39(3):420-1. doi: 10.1212/wnl.39.3.420. No abstract available.

  PMID: 2927653 BACKGROUND

• Personius KE, Pandya S, King WM, Tawil R, McDermott MP. Facioscapulohumeral dystrophy natural history study: standardization of testing procedures and reliability of measurements. The FSH DY Group. Phys Ther. 1994 Mar;74(3):253-63. doi: 10.1093/ptj/74.3.253.

  PMID: 8115459 BACKGROUND

• Thornton CA, Johnson K, Moxley RT 3rd. Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes. Ann Neurol. 1994 Jan;35(1):104-7. doi: 10.1002/ana.410350116.

  PMID: 8285579 BACKGROUND

• Braida C, Stefanatos RK, Adam B, Mahajan N, Smeets HJ, Niel F, Goizet C, Arveiler B, Koenig M, Lagier-Tourenne C, Mandel JL, Faber CG, de Die-Smulders CE, Spaans F, Monckton DG. Variant CCG and GGC repeats within the CTG expansion dramatically modify mutational dynamics and likely contribute toward unusual symptoms in some myotonic dystrophy type 1 patients. Hum Mol Genet. 2010 Apr 15;19(8):1399-412. doi: 10.1093/hmg/ddq015. Epub 2010 Jan 15.

  PMID: 20080938 BACKGROUND

• Guyatt G, Walter S, Norman G. Measuring change over time: assessing the usefulness of evaluative instruments. J Chronic Dis. 1987;40(2):171-8. doi: 10.1016/0021-9681(87)90069-5.

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• Wyrwich KW, Tierney WM, Wolinsky FD. Further evidence supporting an SEM-based criterion for identifying meaningful intra-individual changes in health-related quality of life. J Clin Epidemiol. 1999 Sep;52(9):861-73. doi: 10.1016/s0895-4356(99)00071-2.

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• Guyatt GH, Osoba D, Wu AW, Wyrwich KW, Norman GR; Clinical Significance Consensus Meeting Group. Methods to explain the clinical significance of health status measures. Mayo Clin Proc. 2002 Apr;77(4):371-83. doi: 10.4065/77.4.371.

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• Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989 Dec;10(4):407-15. doi: 10.1016/0197-2456(89)90005-6.

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• Mathai SC, Puhan MA, Lam D, Wise RA. The minimal important difference in the 6-minute walk test for patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2012 Sep 1;186(5):428-33. doi: 10.1164/rccm.201203-0480OC. Epub 2012 Jun 21.

  PMID: 22723290 BACKGROUND

• Teng S, Wang B, Yang F, Yi X, Zhang X, Sun Y. MediDRNet: Tackling category imbalance in diabetic retinopathy classification with dual-branch learning and prototypical contrastive learning. Comput Methods Programs Biomed. 2024 Aug;253:108230. doi: 10.1016/j.cmpb.2024.108230. Epub 2024 May 17.

  PMID: 38810377 BACKGROUND

• Liu P, Liu Y, Liu H, Xiong L, Mei C, Yuan L. A Random Forest Algorithm for Assessing Risk Factors Associated With Chronic Kidney Disease: Observational Study. Asian Pac Isl Nurs J. 2024 Jun 3;8:e48378. doi: 10.2196/48378.

  PMID: 38830204 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be collected to extract genomic DNA from peripheral blood leukocytes. DNA, RNA, and proteins are derived from collected blood and other tissue samples.

MeSH Terms

Conditions

Myotonic Dystrophy; Muscular Dystrophies; Neuromuscular Diseases; Myotonia

Condition Hierarchy (Ancestors)

Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Nicholas Johnson, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Raymond

CONTACT

804-828-6318; Jennifer.raymond@vcuhealth.org

Ruby Langeslay

CONTACT

804-828-6318; Ruby.langeslay@vcuhealth.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 4 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 13, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 1, 2032
• Last Updated: July 27, 2026

Record last verified: 2026-07

Locations

US (1)