DMCRN-02-001: Assessing Pediatric Endpoints in DM1 (ASPIRE-DM1)

February 13, 2024 updated by: Virginia Commonwealth University

Assessing Pediatric Endpoints in DM1 (ASPIRE-DM1)

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.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 4 years (Child)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

30 children with CDM and 20 children with ChDM.

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Congenital Myotonic Dystrophy (CDM)
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)
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?

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
Time Frame: 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.
Through study completion at 18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peabody Developmental Motor Milestones
Time Frame: 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.
Through study completion at 18 months
AIMS
Time Frame: 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.
Through study completion at 18 months
Dysarthria Assessment
Time Frame: Through study completion at 18 months
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
Time Frame: 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.
Through study completion at 18 months
CCMDHI
Time Frame: 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.
Through study completion at 18 months
Domain Delta
Time Frame: 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.
Through study completion at 18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlate the functional outcome measures with potential biomarkers in CDM.
Time Frame: Baseline
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
Blood Sampling
Time Frame: Baseline, month 12, month 18
DNA and RNA samples will be processed by Virginia Commonwealth University.
Baseline, month 12, month 18
Muscle mass, DEXA
Time Frame: Baseline, month 12, month 18
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Investigators

  • Principal Investigator: Nicholas E. Johnson, MD, Virginia Commonwealth University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 24, 2022

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

January 25, 2022

First Submitted That Met QC Criteria

January 25, 2022

First Posted (Actual)

February 4, 2022

Study Record Updates

Last Update Posted (Actual)

February 15, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HM20023386

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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