Tamoxifen Therapy for Myotubular Myopathy
- Conditions
- X Linked Myotubular Myopathy
- Interventions
- Drug: ApoTamox 10mgDrug: Placebo
- Registration Number
- NCT04915846
- Lead Sponsor
- James Dowling
- Brief Summary
This is a phase 1 / 2, randomized, double-blinded, single cross-over study, with a washout period between treatment regimens, to test the efficacy and safety of tamoxifen therapy to improve motor and respiratory function in males with XLMTM.
- Detailed Description
Pre-clinical studies in Mtm1 knockout mice (a model of XLMTM) demonstrated prolonged survival, increased motor function (including muscle strength), and improved muscle histopathology with tamoxifen treatment. Based on these data, and the known safety profile of the drug in humans, we hypothesize that tamoxifen treatment will be safe and will improve motor and respiratory function in XLMTM patients. This is a randomized, double-blinded, single crossover clinical trial to test this hypothesis and determine the safety and efficacy of tamoxifen in improving motor and respiratory function in MTM patients. Each subject will serve as his own control during the placebo phase of the study. As treatments for XLMTM are current not available, this study addresses a critical unmet need by testing a therapy that, if effective, may serve as a primary treatment, or in the future as an adjunct to other therapies in development.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 16
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Drug: ApoTamox 10mg ApoTamox 10mg Drug: Tamoxifen (tamoxifen citrate); ApoTamox 10 mg tablets orally twice daily for 6 months Placebo Placebo Placebo (no active ingredients) tablets orally twice daily for 6 months
- Primary Outcome Measures
Name Time Method Motor Function Measure 32 (MFM32) Baseline to 15 Months Mean change from baseline of Motor Function Measure 32 for subjects aged 4 and older
Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years (CHOP INTEND) Baseline to 15 months Mean change from baseline of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years
10 meter walk test Baseline to 15 months Mean change from baseline in velocity in 10 meter walk test for ambulant participants
- Secondary Outcome Measures
Name Time Method Change in pulmonary function testing scores 4) Maximum Expiratory Pressure Baseline to 15 months Mean change from baseline in participants without invasive respiratory support
Change in pulmonary function testing scores 1) Forced Expiratory Volume in the first second Baseline to 15 months Mean change from baseline in participants without invasive respiratory support
Change in pulmonary function testing scores 2) Forced Vital Capacity Baseline to 15 months Mean change from baseline in participants without invasive respiratory support
Change in pulmonary function testing scores 5) Maximum Inspiratory Pressure or Sniff Inspiratory Pressure Baseline to 15 months Mean change from baseline in participants without invasive respiratory support
Change in pulmonary function testing scores 3) Peak Cough Flow Baseline to 15 months Mean change from baseline in participants without invasive respiratory support
invasive ventilation - time off ventilation Baseline to 15 months Mean change in time off ventilator for participants dependent on invasive respiratory support
Incidence and severity of Adverse Events related to the treatment [ Time Frame: 15 Months ] Baseline to 15 months Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v4.0
micro RNA 133a (miR133a) Baseline to 15 months Assess miR133a as a biomarker of XLMTM
Trial Locations
- Locations (4)
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
National Institutes of Health
🇺🇸Rockville, Maryland, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom