Clinical trial NCT02057705: Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM)
Official title: Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myotubular Myopathy
Keywords: MTM
myotubular myopathy
X-linked centronuclear myopathy
inherited myopathies
neuromuscular diseases
hypotonia
genetic mutation
Lead sponsor: Valerion Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Institut de Myologie, France
name: Genethon
First posted: 2014-02-07
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Investigative Research Centers

Brief summary: This is a prospective, non-interventional, longitudinal study of the natural history and function of approximately 60 patients with MTM from the United States, Canada and Europe. The duration of the study, including the enrollment period, will be 36 months. Data from the study will be used to characterize the disease course of MTM and determine which outcome measures will be the best to assess the efficacy of potential therapies.

Detailed description: This is a prospective, non-interventional, longitudinal study of the natural history and function of patients with MTM. The study duration is 36 months. The enrollment period will be 12 months and each patient will be assessed over 24 months. Data will be analyzed at baseline and annually thereafter and reports will be prepared based on these analyses. A final report will summarize findings after all patients have completed 24 months of follow-up. Assessments performed in this study will be based on the age and ambulatory status of the patient. The assessments will also be adjusted to account for the variability in both phenotypes and age of the patients who may participate in this study. Patients will be evaluated at Baseline, Month 6, Month 12 and Month 24. It is anticipated that approximately 60 patients from the United States, Canada and Europe will be included in this study.

Eligibility criteria: Inclusion criteria:

* Patients of any age (newborns included) may participate.
* Patients over 18 years of age and parent(s)/legal guardian(s) of patients \<18 years of age must provide written informed consent prior to participating in the study and informed assent will be obtained from minors at least 7 years of age when required by regulation.
* MTM resulting from a mutation in the MTM1 gene.
* Male or symptomatic female. A symptomatic female will be defined by the motor function assessment by Motor Function Measure (MFM) or North Star Ambulatory Assessment (NSAA) below 80% of the total score.
* Willing and able to comply with all protocol requirements and procedures.

Exclusion criteria:

* Other disease which may significantly interfere with the assessment of MTM and is clearly not related to the disease.
* Currently enrolled in a treatment study; or treatment with an experimental therapy other than pyridostigmine.

Primary outcomes:
measure: Time to characterize the disease course in MTM patients
timeFrame: Up to 24 Months
Secondary outcomes:
measure: Change in disease severity and disease progression
timeFrame: Baseline, Month 3 (EU only), Month 6, Month 12 and Month 24
Other outcomes:
measure: Number of participants with an immune response against adeno-associated virus (AAV)
timeFrame: Baseline Visit
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital, 300 Longwood Avenue
state: Massachusetts
city: Liège
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Toronto
country: Canada
facility: Hospital for Sick Children, 555 University Avenue
state: Ontario
city: Bron
country: France
facility: Hôpital Femme Mère Enfant, CHU Lyon Escale
city: Lille
country: France
facility: Roger Salengro Hospital, CHU, Lille
city: Lyon
country: France
facility: Croix Rousse Hospital
city: Paris Cedex 13
country: France
facility: Institut de Myologie, GH Pitié Salpêtrière, Bâtiment Babinski
city: Paris
country: France
facility: Hôpital Armand Trousseau
city: Paris
country: France
facility: Institut I-Motion, Hôpital A. Trousseau
city: Toulon
country: France
facility: Hôpital Sainte Musse
city: Essen
country: Germany
facility: University Hospital of Essen
city: Rome
country: Italy
facility: Bambino Gesù Children's Hospital
city: Cadiz
country: Spain
facility: Hôpital Puertas de Mar
Study officials:
affiliation: Valerion Therapeutics, LLC
name: Hal Landy, MD
role: STUDY_DIRECTOR
References:
citation: Herman GE, Finegold M, Zhao W, de Gouyon B, Metzenberg A. Medical complications in long-term survivors with X-linked myotubular myopathy. J Pediatr. 1999 Feb;134(2):206-14. doi: 10.1016/s0022-3476(99)70417-8.
citation: Jungbluth H, Sewry CA, Buj-Bello A, Kristiansen M, Orstavik KH, Kelsey A, Manzur AY, Mercuri E, Wallgren-Pettersson C, Muntoni F. Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation. Neuromuscul Disord. 2003 Jan;13(1):55-9. doi: 10.1016/s0960-8966(02)00194-3.
citation: McEntagart M, Parsons G, Buj-Bello A, Biancalana V, Fenton I, Little M, Krawczak M, Thomas N, Herman G, Clarke A, Wallgren-Pettersson C. Genotype-phenotype correlations in X-linked myotubular myopathy. Neuromuscul Disord. 2002 Dec;12(10):939-46. doi: 10.1016/s0960-8966(02)00153-0.
citation: Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis. 2008 Sep 25;3:26. doi: 10.1186/1750-1172-3-26.
citation: Annoussamy M, Lilien C, Gidaro T, Gargaun E, Che V, Schara U, Gangfuss A, D'Amico A, Dowling JJ, Darras BT, Daron A, Hernandez A, de Lattre C, Arnal JM, Mayer M, Cuisset JM, Vuillerot C, Fontaine S, Bellance R, Biancalana V, Buj-Bello A, Hogrel JY, Landy H, Servais L. X-linked myotubular myopathy: A prospective international natural history study. Neurology. 2019 Apr 16;92(16):e1852-e1867. doi: 10.1212/WNL.0000000000007319. Epub 2019 Mar 22.