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

NCT02057705 | Completed

• 1 other identifier: VAL-101-13
• Study Type: observational
• Target: 48
• Locations: 7 countries
• Sites: 13

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.

Conditions

Myotubular Myopathy

Keywords

MTM; myotubular myopathy; X-linked centronuclear myopathy; inherited myopathies; neuromuscular diseases; hypotonia; genetic mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in disease severity and disease progression

  Baseline, Month 3 (EU only), Month 6, Month 12 and Month 24

Other Outcomes (1)

• Number of participants with an immune response against adeno-associated virus (AAV)

  Baseline Visit

Eligibility Criteria

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

Study Population

Investigative Research Centers

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Valerion Therapeutics, LLC: lead
• Institut de Myologie, France: collaborator
• Genethon: collaborator

Study Sites (13)

Boston Children's Hospital, 300 Longwood Avenue

Boston, Massachusetts, 02115, United States

Location

Centre Hospitalier Regional de la Citadelle

Liège, 4000, Belgium

Location

Hospital for Sick Children, 555 University Avenue

Toronto, Ontario, M5G 1X8, Canada

Location

Hôpital Femme Mère Enfant, CHU Lyon Escale

Bron, 69500, France

Location

Roger Salengro Hospital, CHU, Lille

Lille, 59000, France

Location

Croix Rousse Hospital

Lyon, 69004, France

Location

Hôpital Armand Trousseau

Paris, 75012, France

Location

Institut I-Motion, Hôpital A. Trousseau

Paris, 75012, France

Location

Institut de Myologie, GH Pitié Salpêtrière, Bâtiment Babinski

Paris, 75651, France

Location

Hôpital Sainte Musse

Toulon, 83056, France

Location

University Hospital of Essen

Essen, D-45147, Germany

Location

Bambino Gesù Children's Hospital

Rome, 4-00165, Italy

Location

Hôpital Puertas de Mar

Cadiz, 21-11009, Spain

Location

Related Publications (5)

• 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.

  PMID: 9931531 BACKGROUND

• 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.

  PMID: 12467733 BACKGROUND

• 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.

  PMID: 12467749 BACKGROUND

• 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.

  PMID: 18817572 BACKGROUND

• 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.

  PMID: 30902907 DERIVED

Related Links

• National Institute of Health
• Muscular Dystrophy Association

Biospecimen

Retention: SAMPLES WITH DNA

* 5 ml sample of whole blood will be collected during the study to assess the immunity against various AAV serotypes * 5 ml blood sample may be obtained for peripheral blood mononuclear cells (PBMC) to quantify X-linked myotubular myopathy gene 1 (MTM1) production * 24-hour urine collection will be performed every 6 months in order to measure urinary creatinine excretion * Slides and tissue from a previously performed muscle biopsy will be obtained for a central review and quantification of histo- and immunohistopathological features of MTM

MeSH Terms

Conditions

Myopathies, Structural, Congenital; Neuromuscular Diseases; Muscle Hypotonia

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Hal Landy, MD

  Valerion Therapeutics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2014
• First Posted: February 7, 2014
• Study Start: February 1, 2014
• Primary Completion: June 26, 2017
• Study Completion: June 26, 2017
• Last Updated: June 7, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); DE (1); ES (1); US (1); FR (7); IT (1); BE (1)