DMCRN-02-001: Assessing Pediatric Endpoints in DM1

Recruiting

• Conditions: CHDM; Congenital Myotonic Dystrophy; Childhood Myotonic Dystrophy; CDM

• Registration Number: NCT05224778
• Lead Sponsor: Virginia Commonwealth University

Brief Summary

The overall goal of the study is to establish valid clinical endpoint assessments for children with congenital myotonic dystrophy type 1 and childhood myotonic dystrophy type 1, and develop biomarkers for the condition.

Detailed Description

Myotonic dystrophy type-1 (DM1) is an autosomal dominant disorder caused by a toxic CTG repeat expansion in the 3'UTR of the DMPK gene. DM1 is the most common adult-onset muscular dystrophy, with an overall prevalence of 1:8000. In approximately 10-20% of individuals with DM1, the onset of symptoms occurs at birth, which is known as congenital myotonic dystrophy (CDM). If the onset of symptoms occurs after birth and before age 10, this is known as childhood myotonic dystrophy (ChDM).

Previous studies have enrolled a very limited number of children with CDM and there is very little data to guide disease progression in ChDM.

The rationale for this study is to include a larger population of patients with CDM and ChDM, in order to determine developmental milestones, measures of physical and cognitive function and quality of life, and correlate functional outcome measures with potential biomarkers in CDM and ChDM.

Study Timeline

• Study First Submitted: 2022-01-25
• Study First Submitted QC: 2022-01-25
• Study First Posted: 2022-02-04
• Study Start: 2022-08-24
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-28
• Last Update Posted: 2024-07-01
• Primary Completion: 2026-10
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• CDM group:

  • Age neonate to 3 years 11 months at enrollment.
  • 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 more than 72 hours; and a genetic test confirming an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or mother. 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).
  • Guardian is willing and able to sign consent and follow study procedures

• ChDM Group:

  • Age 1 to 4 years 11 months at enrollment.
  • A diagnosis of ChDM, which is defined as symptoms associated with DM1, absence of symptoms at birth, and a genetic test confirming an expanded trinucleotide (CTG) repeat in the DMPK gene in the child or mother.12 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).
  • Guardian willing and able to sign consent and follow study procedures

Exclusion Criteria

(Both groups)

• Any other non-DM1 illness that would interfere with the ability or results of the study in the opinion of the site investigator
• Significant trauma within one month
• Internal metal or devices (exclusion for DEXA component)
• History of bleeding disorder or platelet count <50,000
• History of reaction to local anesthetic

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate motor milestone attainment in individuals with CDM and ChDM and compare to typically developing children	Through study completion at 18 months	Milestone Assessment using Peabody definitions: This survey would ask parents to assess the age of motor milestones in days, months of infant age. Birth history, including prematurity, ventilatory status, and feeding problems would also be collected on the CRF. Feeding and ventilatory support, as well as height and weight will be collected at each study visit.

Secondary Outcome Measures

Name	Time	Method
Dysarthria Assessment	Through study completion at 18 months	A blinded, standardized video assessment tabulating language milestones by a trained rater will be conducted at each visit.
Vineland	Through study completion at 18 months	The Vineland will be administered by an interviewer to ensure standardized intake of data. This assessment will capture the adaptive function, including gross motor and fine motor, as reported by the parent proxy.
CCMDHI	Through study completion at 18 months	The congenital and childhood myotonic dystrophy health index is a disease specific patient or proxy reported outcome measure specific to these conditions. The current study will utilize the proxy version.
Domain Delta	Through study completion at 18 months	This assessment asks parents for global impression of change related to the baseline visit and will be used as an anchoring measure for the statistical analyses.
Peabody Developmental Motor Milestones	Through study completion at 18 months	This measure captures motor performance up to six years of age. The advantage of this measure is the ability to test against normative values.
AIMS	Through study completion at 18 months	This standardized neurological examination will be performed. It has age adjusted normative values that will be used as controls.

Trial Locations

Locations (5)

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Centro Clinico NeMO; 🇮🇹 Milan, Italy

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

University of Kansas Medical Center; 🇺🇸 Fairway, Kansas, United States