Study of Genotype and Phenotype Characterization in Duchenne Muscular Dystrophy With Small Mutations

NCT05833633 | Unknown

• 1 other identifier: 3791
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Improved standards of care and the regular early use of glucocorticoid treatment have changed the natural history of Duchenne muscular dystrophy (DMD), affecting both survival and time of loss of functional milestones. More recently, there has been increasing evidence of an additional benefit from new therapeutic approaches based on mechanisms targeting specific types of mutation, as Atarulen, authorised in the European Union as Translarna since 31 July 2014 to treat DMD boys with non sense mutations. As there is increasing evidence that specific groups of mutations may have different progression of the disease, it has become mandatory to obtain more detailed long-term information about the patterns of progression related to different genotypes. Natural history of DMD boys carrying deletions has been more studied and less is known about boys carrying small mutations that represent 20% of DMD patients. The aim of this project is to better define the natural history of these patients and to better understand the clinical response to mutation-specific therapies aimed at restoring dystrophin protein production.

Conditions

Muscular Dystrophy, Duchenne

Outcome Measures

Primary Outcomes (4)

• Longitudinal Motor changes in 15 DMD boys with different types of small mutations (Group 1)

  To found in a cohort of 15 patients with different types of small mutations at baseline (T0) and 1 year later (T1) some differences in motor functional assessments including the six minute walking test and the Performance of the Upper Limb.

  1 year

• Longitudinal respiratory changes in 15 DMD boys with different types of small mutations (Group 1)

  To found in the same cohort of 15 patients with different types of small mutations at baseline (T0) and 1 year later (T1) some differences in respiratory data using the Peak Expiratory Flow percentage predicted. ,

  1 year

• Longitudinal Muscle MRI changes in 15 DMD boys with different types of small mutations (Group 1)

  To found in the same cohort of 15 patients with different types of small mutations at baseline (T0) and 1 year later (T1) some differences in muscle MRI scores

  1 year

• Longitudinal genetic changes in 15 DMD boys with different types of small mutations (Group 1)

  To found in the same cohort of 15 patients (prospective cohort) with different types of small mutations at baseline (T0) and 1 year later (T1) some differences in genetic test (urinary stem cells for MiRNA study). Genomic DNA exploring the 5 SNPs associated to the LOA will be collected at T0 only

  1 year

Other Outcomes (4)

• Longitudinal Motor changes in 10 ambulant DMD boys carrying non-sense mutations treated with Traslarna (Group 2)

  1 year

• Longitudinal respiratory changes in 10 ambulant DMD boys carrying non-sense mutations treated with Traslarna (Group 2)

  1 year

• Longitudinal Muscle MRI changes in10 ambulant DMD boys carrying non-sense mutations treated with Traslarna (Group 2)

  1 year

Study Arms (2)

Group of DMD patients with different type of small mutations (Group 1)

Group of DMD patients with different type of small mutations (15 ambulant or not-ambulant patients)

Diagnostic Test: MUSCLE MAGNETIC RESONANCE IMAGING (MRI)

Group of DMD patients with non sense mutations in treatment with Traslarna (Group 2)

Group of 10 ambulant DMD patients with non sense mutations in treatment with Traslarna (3-\[5-(2-fluoro-phenyl)-\[1,2,4\]oxadiazole-3-yl\]-benzoic acid).

Diagnostic Test: MUSCLE MAGNETIC RESONANCE IMAGING (MRI)

Interventions

MUSCLE MAGNETIC RESONANCE IMAGING (MRI) DIAGNOSTIC_TEST

To assess longitudinally at baseline and 1 year later changes on muscle MRI, genetic test, functional motor and respiratory assessments in the DMD group with different type of small mutations and the DMD group with non sense mutations treated with Atarulen in order to better define natural history of these patients. .

Also known as: Genetic exams, Functional motor and respiratory assessments

Group of DMD patients with different type of small mutations (Group 1); Group of DMD patients with non sense mutations in treatment with Traslarna (Group 2)

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

All 25 patients had genetically proven DMD diagnosis with a small mutation genotype; the sample includes both ambulant and non ambulant patients; Ten patients of the 25 are in treatment with Atarulen.

You may qualify if:

• \- DMD diagnosis confirming a small mutation genotype.

You may not qualify if:

• DMD patient enrolled in other clinical trials using genetic approach
• impossibility to perform MRI without sedation
• presence of severe cognitive or behavioral problems

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Claudia Brogna

Rome, 00168, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

this includes: modifier genes associated to the Lost of ambulation; RNA study on the dystrophin transcript in urinary stem cells

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• CLAUDIA BROGNA, MD, PhD

  Fondazione Policlinico Gemelli., IRCCS, Rome, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

CLAUDIA BROGNA

CONTACT

+393208103724; claudia.brogna@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Pediatric Neurologist, MD, PhD, Principal Investigator

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: April 27, 2023
• Study Start: March 18, 2022
• Primary Completion: April 17, 2023
• Study Completion: June 30, 2024
• Last Updated: May 15, 2023

Record last verified: 2023-05

Locations

IT (1)