Clinical trial NCT06276244: Trial Readiness and Endpoint Assessment in Congenital and Childhood Myotonic Dystrophy
Official title: Trial Readiness and Endpoint Assessment in Congenital and Childhood Myotonic Dystrophy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: CDM
ChDM
Keywords: congenital myotonic dystrophy
childhood myotonic dystrophy
Lead sponsor: Fondazione Serena Onlus - Centro Clinico NeMO Milano
Sponsor class: OTHER
Collaborators: name: Bambino Gesù Hospital and Research Institute
name: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: IRCCS Istituto delle Scienze Neurologiche di Bologna
name: IRCCS Fondazione Stella Maris
name: Fondazione Mondino
name: A.O.U. Città della Salute e della Scienza
name: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
name: Istituto Giannina Gaslini
First posted: 2024-02-23
Enrollment: 70
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Please refer to the inclusion and exclusion criteria.

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.

Detailed description: observational prospective study

Eligibility criteria: Inclusion criteria, 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 (\&lt;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\&gt;1,500).

Inclusion criteria, 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.

Exclusion criteria, CDM and ChDM groups:

1. Any other non-DM1 illness that would interfere with the ability or results of the study in the opinion of the site investigator
2. Significant trauma within one month
3. Internal metal or devices (exclusion for DEXA component)
4. Unable to walk more than 50 feet if over the age of 3.

Primary outcomes:
measure: Physical function
timeFrame: From Baseline (T0) to Days 1080
measure: Physical function
timeFrame: From Baseline (T0) to Days 1080
measure: Cognitive-behavioral and Quality of Life
timeFrame: From Baseline (T0) to Days 1080
measure: Cognitive-behavioral and Quality of Life
timeFrame: From Baseline (T0) to Days 1080
measure: Biomarkers
timeFrame: From Baseline (T0) to Days 1080
measure: Biomarkers
timeFrame: From Baseline (T0) to Days 1080
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione Serena Onlus - Centro Clinico NeMO Milano
Study officials:
References: