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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06337669
Other study ID # OSRSCP-GUP21006
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date January 31, 2022
Est. completion date January 31, 2025

Study information

Verified date March 2024
Source IRCCS San Raffaele
Contact Stefano C Previtali, MD
Phone 00390226433036
Email neuromuscolare@hsr.it
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


Description:

The primary clinical endpoint is time to loss of ambulation (LOA). Secondary endpoints include: 1. The change over time of the following functional measurements: 1.1 Motor function: The 6 Minute Walk test (6MWT) and North Star Ambulatory Assessment (NSAA) including sub-items such as Time to Rise from the floor. 1.2 Respiratory function: Forced Vital Capacity (FVC) Liters (L) and % of predicted; time to FVC% < 50%. Time to Nocturnal Ventilation initiation. 1,3 Cardiac function: Left ventricular ejection fraction (EF) as measured by echocardiogram. 2. To characterize DNA breakpoints in mild vs severe phenotypes


Recruitment information / eligibility

Status Recruiting
Enrollment 26
Est. completion date January 31, 2025
Est. primary completion date January 31, 2025
Accepts healthy volunteers No
Gender Male
Age group N/A and older
Eligibility Inclusion Criteria: - pediatric and adult DMD patients harboring a genetically confirmed duplication of the exon 2 in the dystrophin gene Exclusion Criteria: - patients lacking genetic confirmation of Dup2 mutation

Study Design


Related Conditions & MeSH terms


Locations

Country Name City State
Italy Dept. of Neurology, IRCCS Ospedale San Raffaele Milano

Sponsors (1)

Lead Sponsor Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Age at loss of ambulation Age at loss of ambulation 12 months
Secondary Time test for motor function The 6 Minute Walk test (6MWT) and North Star Ambulatory Assessment (NSAA) including sub-items such as Time to Rise from the floor. 12 months
Secondary Respiratory function Forced Vital Capacity (FVC) Liters (L) and % of predicted; time to FVC% < 50%. Time to Nocturnal Ventilation initiation 12 months
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