Myotubular myopathy Nervous System Diseases Congenital myopathies
Conditions
Interventions
Method of randomisation:
Once a patient has been confirmed as eligible for the study, the Enrollment section of the Patient Enrollment application will be completed and submitted to Ozmosis Research.
Sponsors
Hospital for Sick Children
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Male 2. Patients aged 2 years and older may participate 3. MTM resulting from a confirmed mutation in the MTM1 gene 4. 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, or at least 7 years of age when required by regulation 5. Willing and able to comply with all protocol requirements and procedures
Exclusion criteria
Exclusion criteria: An individual who meets any of the following criteria will be excluded from participation in this study: 1. Other disease which may significantly interfere with the assessment of MTM and is clearly not related to the disease, at the discretion of the qualified investigator 2. Has undergone surgery or hospitalisation < 3 months before starting TAM4MTM (at t = -3 months), or has surgery scheduled during the 18 months of participation in TAM4MTM, which will impede motor assessments in the opinion of the Investigator 3. Has a history of thromboembolic events 4. Has severe liver dysfunction 5. Currently enrolled in a treatment study for XLMTM or receiving treatment with an experimental therapy other than pyridostigmine 6. Treatment with pyridostigmine for < 6 weeks duration (must be greater than 6 weeks to be included in TAM4MTM) 7. Use of concomitant medication known to inhibit CYP2D6 and/or CYP3A4, including clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit, paroxetine, troleandomycin, rifampin, phenobarbital, aminoglutethimidine, medroxyprogesterone, amiodarone, haloperidol, indinavir, ritonavir, quinidine, rifampicin, or any selective serotonin reuptake inhibitor (SSRI) 8. Subject has a contraindication to tamoxifen or its ingredients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measured at screening (month -3), months 0, 3, 6, 9, 12, 15: 1. The safety and tolerability of tamoxifen therapy in males with XLMTM. This will be done by monitoring participants closely once they start IP dosing from Month 0-6 (phase 1), Washout Month 7-9 and Month 10-15 (phase 2) 2.1. Motor function measured using Motor Function Measure 32; if the participant is under the age of 4 years, both Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-Intend) and MFM32 will be performed 2.2. For ambulant patients: 10-metre walk test (10MWT) in addition to MFM32 | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured at screening (month -3), months 0, 3, 6, 9, 12, 15. TAM4MTM Survey will be conducted over the telephone monthly between clinic visits: 1. Respiratory function measured using: 1.1. Standardized pulmonary function tests (PFTs): 1.1.1. Patients not completely dependent on mechanical ventilation, without a tracheostomy: forced expiratory volume in the first second exhalation (FEV1), forced vital capacity (FVC), peak cough flow (PCF), maximum expiratory pressure (MEP), maximum inspiratory pressure (MIP) or sniff nasal inspiratory pressure (SNIP) 1.1.2. Patients with tracheostomy and dependent on mechanical ventilation: time off ventilation before oxygen saturation reaches 94%, or when participant shows distress 1.2. Type of respiratory support (non-invasive or invasive), and length of time used per day 1.3. Length of time (minutes or hours) off mechanical respiratory support per day 2. Vital signs: body temperature, heart rate, respiratory rate, systolic and diastolic blood pressure and oxygen saturation will be measured, as well as weight and length/height. Performed by qualified site staff. 3. Physical Exam: includes range of eye motion (horizontal and vertical) and ptosis. Performed by the PI or qualified site staff. 4. Blood collection/sampling by venepuncture and results analysed by the local labs. Sex-hormone lab results will be sent to the study coordinator at SickKids for review. Sera will be aliquoted and sent to Sickkids for pharmacokinetic and biomarker analysis. 5. Ophthalmological assessment performed by an ophthalmologist or optometrist) for Healthy Eye Check. Any abnormalities should be noted. Participants’ eyes will also be checked for cataracts. 6. Electrocardiogram (ECG): as a safety measure, ECGs with Q-T measurement will be conducted at every study visit. ECG will be taken using an ECG machine to check the electrical activity of the heart. 7. Abdominal ultrasound performed by qualified site staff using an ultrasound machine. Any abnormal hepa | — |
Countries
England, United Kingdom
Outcome results
None listed