DMCRN-02-001: Assessing Pediatric Endpoints in DM1

Study Overview
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Brief Summary
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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
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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.

Official Title
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Assessing Pediatric Endpoints in DM1 (ASPIRE-DM1)

Conditions
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Congenital Myotonic Dystrophy, Childhood Myotonic Dystrophy, CDM, CHDM

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 59 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Congenital Myotonic Dystrophy (CDM)<br>CDM group includes those aged neonate to 3 years, 11 months at enrollment. Individuals must have 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). | |
| Childhood Myotonic Dystrophy (ChDM)<br>ChDM group includes those aged 1 to 4 years, 11 months at enrollment. Individuals must have 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. 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). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate motor milestone attainment in individuals with CDM and ChDM and compare to typically developing children | 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. | Through study completion at 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peabody Developmental Motor Milestones | This measure captures motor performance up to six years of age. The advantage of this measure is the ability to test against normative values. | Through study completion at 18 months | 
| AIMS | This standardized neurological examination will be performed. It has age adjusted normative values that will be used as controls. | Through study completion at 18 months | 
| Dysarthria Assessment | A blinded, standardized video assessment tabulating language milestones by a trained rater will be conducted at each visit. | Through study completion at 18 months | 
| Vineland | 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. | Through study completion at 18 months | 
| CCMDHI | 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. | Through study completion at 18 months | 
| Domain Delta | 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. | Through study completion at 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Research, Childhood myotonic dystrophy, Myotonic dystrophy, Congenital Myotonic Dystrophy, CDM, ChDM