The primary aim of this study is to document with quantified measurements the natural history of Duchenne Muscular Dystrophy. Several validated tools will be used to describe motor, orthopedic and respiratory functions, and quality of life along a 6…
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Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Muscle disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Functional tests assessing pulmonary function and upper- and lower limb
performance. These includes spirometry (FVC, MIP, MEP, PEF, Peak cough flow),
timed and graded functional tests, 6 minute walk test (6MWT) , NorthStar
Ambulatory Assessment (NSAA), myometry and goniometry, and PUL assessment.
Furthermore, questionnaires regarding quality of life and disease specific
milestones will be filled out.
Secondary outcome
Occurrence of antidystrophin antibodies in serum and autoreactive T-cells to
dystrophin during the course of the disease in relation to functional outcome
measures. Proteomics in serum and urine to search for disease biomarkers.
Genome wide SNP analysis.
Background summary
Duchenne Muscular Dystrophy (DMD) is a fatal X-linked inherited muscle
disorder, affecting 1 in 3,600 live male births. It classically presents in the
first decade with proximal muscle weakness, which leads to progressive loss of
ambulation before the age of 13 years. DMD occurs as a result of mutations in
the dystrophin gene on chromosome Xp21. Characteristically, the muscle enzyme
serum creatinine kinase is markedly increased and muscle biopsy shows absent
dystrophin protein. To date there is no cure. In the recent years, there have
been promising advances for new potential genetic treatments (including the
development of exon skipping with anti-sense oligomers producing dystrophin
restoration). Because of the relative rarity of the disease and its progression
over many years, it is not always feasible to test these potential therapies in
randomized, blinded and placebo controlled trials. Therefore, it is required to
expand our understanding on the natural history of DMD and to develop outcome
measures, especially for the more advanced stages of the disease. In the last
years, genetic modifiers have been identified in other genes than the DMD gene
that influence the course of the disease.
Study objective
The primary aim of this study is to document with quantified measurements the
natural history of Duchenne Muscular Dystrophy. Several validated tools will be
used to describe motor, orthopedic and respiratory functions, and quality of
life along a 6 years follow-up study in ambulant and non-ambulant patients.
Objective is to determine the most sensitive outcome measures to use in the
assessment of efficacy of future therapies. Secondary objectives are to
understand how specific dystrophin responses are to DMD and to search for
disease biomarkers in blood and urine.
Study of genetic disease modifiers in the DNA.
Study design
This prospective longitudinal natural history study will be performed in two
cohorts of patients with DMD according to their level of functional motor
ability (ambulant/non-ambulant). This study is designed as a large
multi-institution study including 6 centres in 3 European countries:
Netherlands (Leiden and Nijmegen), France (Paris) and UK (London (2 centres)
and Newcastle).
Study burden and risks
The burden for patients and their families are six extra visits to the clinic
in 6 years taking up to 1,5 hours, answering a quality of life questionnaire
taking 5 minutes. The optional study of disease modifiers will be done via a
SNP analysis on stored DNA. No incidental findings are to be expected.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
NON AMBULANT DMD PATIENTS
1. Children, teenagers and adults from the age of 5 with DMD, who have lost the
ability to walk 10 meters with no support
2. The diagnosis of DMD must be documented by genetic testing.
3. Patients should preferably have deletions amenable of skipping of exons 51
or 53 or 45 or 44 or 46 or 50 or 52.
4. Patients should be capable of sitting upright in a wheelchair for at least
an hour
5. Patients should be stable from a respiratory point of view., AMBULANT DMD
PATIENTS
Inclusion criteria:
1. Ambulant children from 5 years old and teenagers with DMD, and potential
candidates for future genetic therapies with antisense oligomer (AO) exon
skipping
2. The diagnosis of DMD must be documented by MLPA or a standard genetic test
for the disorder, genotypically confirmed to have an out-of-frame deletion(s)
that could be corrected by skipping exon 51 or 53 or 45 or 44 or 46 or 50 or 52
(Table1).
3. Ability to walk independently for at least 10 meters at recruitment.
4. Patients should receive the standard of care for DMD as recommended by the
NorthStar UK and TREAT-NMD (ie: on glucocorticoids treatment)
5. Sufficiently preserved pulmonary function (FVC >30%) and absence of symptoms
of cardiac failure.
Exclusion criteria
NON AMBULANT DMD PATIENTS:, 1. Patients who are currently involved in
interventional clinical trials aimed at restoring dystrophin will be excluded,
as their data could not be used to establish natural history of the disease
(participation in a previous interventional clinical trial prior to 6 months
from being recruited in the study is not an exclusion criterion)
2. Patients with severe intellectual impairment, who would be unable to
cooperate with examination
3. Patients/families we anticipate may have emotional/ psychological problems
if recruited in into a natural history study
4. Symptomatic cardiac failure
5. Recent (< 6 months) upper limb surgery or trauma
6. Anticipated surgery for anytime during the duration of the study
7. For the MRI substudy, patients with metal/metallic surgically inserted
equipment incompatible with MRI scan and patients suffering from claustrofobia.
, AMBULANT DMD PATIENTS:, 1. Patients who are currently involved in
interventional clinical trials aimed at restoring dystrophin will be excluded,
as their data could not be used to establish natural history of the disease
(participation in a previous interventional clinical trial prior to 6 months
from being recruited in the study is not an exclusion criterion)
2. Patients with severe intellectual impairment, who would be unable to
cooperate with examination
3. Patients/families we anticipate may have emotional/ psychological problems
if recruited in into a natural history study
4. Recent surgery or anticipated for anytime during the duration of the study
5. For the MRI substudy, patients with metal/metallic surgically inserted
equipment incompatible with MRI scan and patients suffering from claustrofobia.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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In other registers
| Register | ID |
|---|---|
| CCMO | NL51560.058.14 |