DMCRN-02-001: Assessing Pediatric Endpoints in DM1

Congenital Myotonic Dystrophy Clinical Trial

— ASPIRE-DM1  

Official title:

Assessing Pediatric Endpoints in DM1 (ASPIRE-DM1)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05224778
• Other study ID #: HM20023386
• Status: Recruiting
• Start date: August 24, 2022
• Est. completion date: December 2026

Study information

• Verified date: February 2024
• Source: Virginia Commonwealth University
• Contact: Ruby Langeslay
• Phone: 804-828-8481
• Email: ruby.langeslay[@]vcuhealth.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2026
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 59 Months

Eligibility

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

Related Conditions & MeSH terms

• Congenital Myotonic Dystrophy
• Myotonic Dystrophy

Locations

Country	Name	City	State
Italy	Centro Clinico NeMO	Milan
United States	University of Kansas Medical Center	Fairway	Kansas
United States	University of Iowa	Iowa City	Iowa
United States	University of California, Los Angeles	Los Angeles	California
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Rochester Medical Center	Rochester	New York
United States	Stanford University	San Carlos	California

Sponsors (1)

Lead Sponsor	Collaborator
Virginia Commonwealth University

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlate the functional outcome measures with potential biomarkers in CDM.	Fine needle muscle biopsy:On the baseline visit, a fine needle aspirate will be performed. Biopsy will only be peformed once to minimize the risk. The procedure will be performed with local anesthesia (1% lidocaine without epinephrine and free of preservatives) of the vastus lateralis. Following lidocaine injection, a fine needle will be used to aspirate the quadriceps muscle to obtain a total of one aspirate. The aspirate will be flash frozen in liquid nitrogen. A similar procedure has been performed on adults with DM1, and the average biopsy yields sufficient tissue for RNA-Seq analysis.	Baseline
Other	Blood Sampling	DNA and RNA samples will be processed by Virginia Commonwealth University.	Baseline, month 12, month 18
Other	Muscle mass, DEXA	Lean muscle mass will be evaluated using serial DEXA scans as an exploratory endpoint. All sites will use a Hologic DEXA scanner. Investigators will evaluate whole body lean mass, left and right arm lean mass, and left and right leg lean mass. Particularly early in childhood, investigators would expect rapid changes in lean muscle mass. If there were a divergence between controls and subjects with CDM, this would provide evidence that CDM is a disorder of muscle maturity, as well as provide a potential biomarker.	Baseline, month 12, month 18
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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