Characterization of DupEx2 Duchenne Muscular Dystrophy

NCT06337669 | Recruiting

• 1 other identifier: OSRSCP-GUP21006
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

To characterize the clinical phenotype and possible predictive/prognostic factors of patients with Duchenne muscular dystrophy (DMD) due to duplication of exon 2 (Dup2). Specifically, we aim 1) to describe the progression of motor, respiratory and cardiac function; 2) to enquire if the phenotypic spectrum of Dup2 is milder than classic DMD, 3) to perform whole genome sequencing (WGS) to characterize DNA breakpoints to correlate with the phenotype; 4) to collect material for future proteomic/transcriptomic studies. Background/Rationale DMD is caused by mutations in the DMD gene and in 11% of cases is due to duplications. The most promising therapeutic approaches include mutation-specific therapies. Notably, there is increasing evidence that specific groups of mutations may underlie different disease trajectories compared to the "average" DMD population. It is thus mandatory to have more information on genotype-phenotype correlations and patterns of progression related to different genotypes. Dup2 is the most common DMD duplication and the only one for which a AAV-mediated exon skipping study is ongoing. Despite most case series and databases ascribe Dup2 to severe phenotype, our preliminary findings sustain that these patients have collectively a milder progression of the disease and in 1/3 of cases a significantly milder phenotype. Moreover, our attempts to reveal mechanism involved in attenuating the phenotype would confute the hypothesis of alternative spicing transcripts as previously described for DMD with deletion of exon 2. Research design and methods Clinical information regarding a cohort of 26 Italian Dup2 patients will be collected. Differences in time to loss of ambulation compared to a DMD control group will be achieved. Finally, we will retrieve DNA for correlative WGS studies. Anticipated output We expect that Dup2 patients present a milder DMD phenotype , which might be predicted by genomic studies.

Conditions

Muscular Dystrophy, Duchenne

Outcome Measures

Primary Outcomes (1)

• Age at loss of ambulation

  Age at loss of ambulation

  12 months

Secondary Outcomes (2)

• Time test for motor function

  12 months

• Respiratory function

  12 months

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Italian DMD patients with Dup2 mutation

You may qualify if:

• pediatric and adult DMD patients harboring a genetically confirmed duplication of the exon 2 in the dystrophin gene

You may not qualify if:

• patients lacking genetic confirmation of Dup2 mutation

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Dept. of Neurology, IRCCS Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample for genomic analysis

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

• Stefano C Previtali, MD

  IRCCS Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stefano C Previtali, MD

CONTACT

00390226433036; neuromuscolare@hsr.it

Alberto A Zambon, MD

CONTACT

00390226431; neuromuscolare@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Neuromuscular Repair Unit

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 29, 2024
• Study Start: January 31, 2022
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: March 29, 2024

Record last verified: 2024-03

Locations

IT (1)