Trial Readiness and Endpoint Assessment in Congenital and Childhood Myotonic Dystrophy

NCT06276244 | Completed

• 1 other identifier: NM040-GUP19002
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Children with congenital myotonic dystrophy (CDM) present at birth with respiratory insufficiency, talipes equinovarus, feeding difficulties and hypotonia. There is a 30% mortality rate in the first year of life. Children with childhood onset myotonic dystrophy present with symptoms later on but soon develop behavioural difficulties and learning difficulties and are at risk for autistic features and gastrointestinal symptoms. The ability to conduct a therapeutic trial in children with CDM or ChDM is directly limited by the lack of available data regarding appropriate clinical endpoints and biomarkers. Whereas there is an active Italian collaboration recruiting adults with DM1 to study muscle and multisystem aspects in this population, there is no active network in Italy involved in the pediatric population with DM1. Though the underlying mechanism is the same in adult DM1, in CDM and ChDM there are specific challenges to the pediatric population. The aim of this project is to coordinate the Italian Child Neurologist actively involved with CDM and ChDM in a common effort of standardizing protocols and procedures to be applied in the care of these patients. Specific aims are to collect functional measures and clinical information over time to define clinically meaningful endpoints and outcome measures in preparation for international therapeutic clinical trials. This project will contribute to the ongoing international study in CDM by recruiting additional patients from all over Italy and will extend the investigations to the childhood onset forms as an additional add-on pilot study in view of potential treatment options. The investigators expect that the Italian network, with Telethon support, will provide the necessary backbone for trial readiness in the pediatric population both at the national and international levels.

Conditions

CDM; ChDM

Keywords

congenital myotonic dystrophy; childhood myotonic dystrophy

Outcome Measures

Primary Outcomes (6)

• Physical function

  Measures of right grip strength using hand-held myometry

  From Baseline (T0) to Days 1080

• Physical function

  Oral facial strength as measured by lip-force meter

  From Baseline (T0) to Days 1080

• Cognitive-behavioral and Quality of Life

  Total score and subscores from the CCMDHI

  From Baseline (T0) to Days 1080

• Cognitive-behavioral and Quality of Life

  BRIEF total scores

  From Baseline (T0) to Days 1080

• Biomarkers

  Muscle RNA splicing changes

  From Baseline (T0) to Days 1080

• Biomarkers

  Lean muscle mass

  From Baseline (T0) to Days 1080

Study Arms (2)

Congenital Myotonic Dystrophy (CDM)

CDM group: 1. Age 0-17 years, 11 months of age 2. 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 Muscular Dystrophy (ChDM)

ChDM group: 1. Age 0-17 years, 11 months of age 2. A diagnosis of ChDM, which is defined as children having symptoms of myotonic dystrophy after day 30 from birth. These may include any delay in psychomotor development, attention deficit disorder, behavioral abnormalities within the spectrum of autistic spectrum disorders, gastrointestinal dysfunction such as persistent constipation or diarrhea and gastroesophageal reflux; 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.

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Please refer to the inclusion and exclusion criteria.

You may qualify if:

• Age 0-17 years, 11 months of age
• 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).
• Age 0-17 years, 11 months of age
• A diagnosis of ChDM, which is defined as children having symptoms of myotonic dystrophy after day 30 from birth. These may include any delay in psychomotor development, attention deficit disorder, behavioral abnormalities within the spectrum of autistic spectrum disorders, gastrointestinal dysfunction such as persistent constipation or diarrhea and gastroesophageal reflux; 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.

You may not qualify if:

• 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
• Unable to walk more than 50 feet if over the age of 3.

Sponsors & Collaborators

• Fondazione Serena Onlus - Centro Clinico NeMO Milano: lead
• Bambino Gesù Hospital and Research Institute: collaborator
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: collaborator
• IRCCS Istituto delle Scienze Neurologiche di Bologna: collaborator
• IRCCS Fondazione Stella Maris: collaborator
• Fondazione Mondino: collaborator
• A.O.U. Città della Salute e della Scienza: collaborator
• Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta: collaborator
• Istituto Giannina Gaslini: collaborator

Study Sites (1)

Fondazione Serena Onlus - Centro Clinico NeMO Milano

Milan, 20162, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

PAX-gene

MeSH Terms

Conditions

Myotonic Dystrophy

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2024
• First Posted: February 23, 2024
• Study Start: July 8, 2020
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: July 5, 2024

Record last verified: 2024-07

Locations

IT (1)