Clinical trial NCT01840657: Myotubular Myopathy Event Study
Official title: Prospective Study of Adverse Event Rates in Males With X-Linked Myotubular Myopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: X-linked Myotubular Myopathy
Keywords: CMDIR (Congenital Muscle Disease International Registry)
X-linked myotubular myopathy
centronuclear myopathy
myotubularin
MTM1 gene
mutation
survival
adverse event
disease complication
hospital admission
emergency room visit
motor function
respiratory function
natural history study
Lead sponsor: Cure CMD
Sponsor class: OTHER
Collaborators: name: Congenital Muscle Disease International Registr
name: University of Michigan
First posted: 2013-04-26
Enrollment: 33
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants for the MTM Event study will be recruited from 2 sources:

* the Centronculear Myopathy Natural History Study and
* the Congenital Muscle Disease International Registry (CMDIR)

Brief summary: X-Linked myotubular myopathy (XLMTM), a form of centronuclear myopathy (CNM) is the result of a mutation in the MTM1 (myotubularin) gene which leads to altered myotubularin. Myotubularin is essential for optimum muscle function. To date, over 100 mutations have been described resulting in a range of disease onset and symptom severity. The early onset form presents with neonatal hypotonia, muscle weakness, respiratory distress and an ongoing requirement for continuous ventilatory support with the inability to maintain a sitting position once placed. Males with both later onset and milder symptoms usually do not require ongoing ventilatory support, achieve a higher maximal motor function with ability to sit when placed and even walk, and have improved survival rates. Males with XLMTM may experience complications (events) at birth and throughout their lifetime. The goal of the study is to identify the number of events over twelve months in males with genetically confirmed XLMTM. Parents or affected individuals over the age of 18 years who are able to access telephone will provide answers to an established event survey to evaluate the frequency and types of events. Emergency department, hospital admissions and mortality will be confirmed by obtaining medical reports.

The investigators hypothesize that there will be no association between the frequency of events and markers of clinical severity including the need for ventilatory support at birth, current level of ventilatory support (no support, support less than 12 hours, support more than 12 hours) and current motor function (walking, sitting without support, inability to sit without support).


Eligibility criteria: Inclusion Criteria:

* males with a confirmed MTM1 mutation OR
* males with a muscle biopsy consistent with myotubular myopathy AND family history consistent with X-linked inheritance AND
* English-speaking parent/guardian of a living male child or a decisionally impaired adult OR English-speaking affected male over 18 years of age who can access telephone
* signed study consent
* enrolled in the Congenital Muscle Disease International Registry (CMDIR)

Exclusion Criteria:

* males with only a clinical diagnosis of XLMTM but without family history of XLMTM
* an affected male who has a genetically confirmed form of centronuclear myopathy (CNM) that is not caused by a mutation in the MTM1 gene
* females with MTM1 due to the limited number of females affected and the variability of clinical presentation

Primary outcomes:
measure: Survey of a defined set of events
timeFrame: 12 months
measure: Frequency of a predefined set of events related to ventilatory status
timeFrame: 12 months
measure: Frequency of a predefined set of events related to current motor function
timeFrame: 12 months
Secondary outcomes:
measure: Association between event frequency and genotype
timeFrame: 12 months
measure: Association between event rate and season
timeFrame: 12 months
Other outcomes:
Locations:
city: Torrance
country: United States
facility: CMDIR
state: California
Study officials:
affiliation: University of Michigan
name: Joseph Hornyak, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cure CMD
name: Anne Rutkowski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan
name: James Dowling, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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