Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM) (MTM)

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.

Study Overview

• Status: Completed
• Conditions: Myotubular Myopathy

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.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium, 4000
    • Centre Hospitalier Régional de la Citadelle
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children, 555 University Avenue
• France
  • Bron, France, 69500
    • Hôpital Femme Mère Enfant, CHU Lyon Escale
  • Lille, France, 59000
    • Roger Salengro Hospital, CHU, Lille
  • Lyon, France, 69004
    • Croix Rousse Hospital
  • Paris, France, 75012
    • Hôpital Armand Trousseau
  • Paris, France, 75012
    • Institut I-Motion, Hôpital A. Trousseau
  • Paris Cedex 13, France, 75651
    • Institut de Myologie, GH Pitié Salpêtrière, Bâtiment Babinski
  • Toulon, France, 83056
    • Hopital Sainte Musse
• Germany
  • Essen, Germany, D-45147
    • University Hospital of Essen
• Italy
  • Rome, Italy, 4-00165
    • Bambino Gesu Children's Hospital
• Spain
  • Cadiz, Spain, 21-11009
    • Hôpital Puertas de Mar
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital, 300 Longwood Avenue

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Investigative Research Centers

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to characterize the disease course in MTM patients	Study-specific functional assessments and patient questionnaires will be used and will be based on the age and ambulatory status of the participant	Up to 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in disease severity and disease progression	Study-specific functional assessments and patient questionnaires will be used and will be based on the age and ambulatory status of the participant	Baseline, Month 3 (EU only), Month 6, Month 12 and Month 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with an immune response against adeno-associated virus (AAV)	A 5 ml sample of whole blood will be collected during the study to assess the immunity against various AAV serotypes.	Baseline Visit

Collaborators and Investigators

• Sponsor: Valerion Therapeutics, LLC
• Collaborators: Institut de Myologie, France; Genethon
• Investigators: Study Director: Hal Landy, MD, Valerion Therapeutics, LLC

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• National Institute of Health
• Muscular Dystrophy Association

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): June 26, 2017
• Study Completion (Actual): June 26, 2017

Study Registration Dates

• First Submitted: February 4, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): June 7, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: hypotonia; myotubular myopathy; MTM; X-linked centronuclear myopathy; inherited myopathies; neuromuscular diseases; genetic mutation
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Muscular Diseases; Myopathies, Structural, Congenital
• Other Study ID Numbers: VAL-101-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No