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TerminatedNCT04915846TAM4MTMUpdated Sep 19, 2024

Tamoxifen Therapy for Myotubular Myopathy

A Phase 1/2 interventional study of ApoTamox 10mg and Placebo in X Linked Myotubular Myopathy, sponsored by James Dowling. Terminated at 4 sites in 3 countries. Open to male participants aged 6 Months and older. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by James Dowling · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Study terminated due to safety concerns.

From the registry’s dates

  • Primary completion was May 2024, 2 years 4 months ago, and no results have been posted to the registry.
  • Registered 4 months after the study started (first participant enrolled Dec 2020, registered May 2021).
Phase
Phase 1/2
Study type
Interventional
Enrollment
6
Allocation
Randomized
Ages
6 Months and older
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • X Linked Myotubular Myopathy

Keywords

  • tamoxifen
  • X-linked myotubular myopathy
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In context

Muscular Diseases

280 studies on the registry are indexed under Muscular Diseases; 63 are open to participants now.

This study's enrollment of 6 is below the median of 34 across 157 interventional studies indexed under Muscular Diseases.

Browse Muscular Diseases studies →

Lead sponsor

This is the only study on the registry with James Dowling as lead sponsor.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
6 Months and older
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

  1. Male
  2. Patients ages 6 months and older may participate.
  3. XLMTM resulting from a confirmed mutation in the Myotubularin 1 (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

  1. Other disease which may significantly interfere with the assessment of myotubular myopathy (MTM) and is clearly not related to the disease, at the discretion of the qualified investigator.
  2. Has undergone surgery or hospitalization \< 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. Currently enrolled in a treatment study for XLMTM or receiving treatment with an experimental therapy other than pyridostigmine.
  5. Treatment with pyridostigmine for \< 6 weeks duration (must be greater than 6 weeks to be included in TAM4MTM).
  6. 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, aminoglutethimide, medroxyprogesterone, amiodarone, haloperidol, indinavir, ritonavir, quinidine, rifampicin, or any selective serotonin reuptake inhibitor (SSRI).
  7. Subject has a contraindication to tamoxifen or its ingredients
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
6 participants (actual)

Study arms

  • Experimental
    Drug: ApoTamox 10mg

    Drug: Tamoxifen (tamoxifen citrate); ApoTamox 10 mg tablets orally twice daily for 6 months

    Drug: ApoTamox 10mg

  • Placebo comparator
    Placebo

    Placebo (no active ingredients) tablets orally twice daily for 6 months

    Drug: Placebo

Interventions

  • DrugApoTamox 10mg

    All participants will receive tamoxifen (ApoTamox) for approximately 6 months (6 months + 1 week). Participants and study staff will be blinded as to whether the participants are starting with the placebo or the drug. Depending on randomization, drug or placebo will be dispensed at the end of the t=0 study visit (Phase 1). Dosing will commence the day after the t=0 study visit. At the end of Phase 1, participants will enter a 'washout' period, when they will cease treatment. After approximately 3 months of washout, participants will cross-over to the other treatment regimen and receive the other interventional product (IP) for the final 6 months of their study participation (Phase 2).

    Also known as: Tamoxifen Citrate

  • DrugPlacebo

    placebo comparator

06

What researchers measure

Primary outcomes

  1. Motor Function Measure 32 (MFM32)

    Mean change from baseline of Motor Function Measure 32 for subjects aged 4 and older

    Time frame: Baseline to 15 Months

  2. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years (CHOP INTEND)

    Mean change from baseline of Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for subjects aged 2-4 years

    Time frame: Baseline to 15 months

  3. 10 meter walk test

    Mean change from baseline in velocity in 10 meter walk test for ambulant participants

    Time frame: Baseline to 15 months

Secondary outcomes

  1. Change in pulmonary function testing scores 1) Forced Expiratory Volume in the first second

    Mean change from baseline in participants without invasive respiratory support

    Time frame: Baseline to 15 months

  2. Change in pulmonary function testing scores 2) Forced Vital Capacity

    Mean change from baseline in participants without invasive respiratory support

    Time frame: Baseline to 15 months

  3. Change in pulmonary function testing scores 3) Peak Cough Flow

    Mean change from baseline in participants without invasive respiratory support

    Time frame: Baseline to 15 months

  4. Change in pulmonary function testing scores 4) Maximum Expiratory Pressure

    Mean change from baseline in participants without invasive respiratory support

    Time frame: Baseline to 15 months

  5. Change in pulmonary function testing scores 5) Maximum Inspiratory Pressure or Sniff Inspiratory Pressure

    Mean change from baseline in participants without invasive respiratory support

    Time frame: Baseline to 15 months

  6. invasive ventilation - time off ventilation

    Mean change in time off ventilator for participants dependent on invasive respiratory support

    Time frame: Baseline to 15 months

  7. Incidence and severity of Adverse Events related to the treatment [ Time Frame: 15 Months ]

    Incidence of serious adverse events and adverse events throughout the study, as assessed by CTCAE v4.0

    Time frame: Baseline to 15 months

  8. micro RNA 133a (miR133a)

    Assess miR133a as a biomarker of XLMTM

    Time frame: Baseline to 15 months

07

Study locations

4 sites
  • Ann and Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • National Institutes of Health
    Rockville, Maryland 20892, United States
  • Hospital for Sick Children
    Toronto, Ontario M5G1X8, Canada
  • Great Ormond Street Hospital for Children
    London, WC1N 3JH, United Kingdom
08

References and documents

Publications

  • Amburgey K, Tsuchiya E, de Chastonay S, Glueck M, Alverez R, Nguyen CT, Rutkowski A, Hornyak J, Beggs AH, Dowling JJ. A natural history study of X-linked myotubular myopathy. Neurology. 2017 Sep 26;89(13):1355-1364. doi: 10.1212/WNL.0000000000004415. Epub 2017 Aug 25. PubMed 28842446 ↗
  • Maani N, Sabha N, Rezai K, Ramani A, Groom L, Eltayeb N, Mavandadnejad F, Pang A, Russo G, Brudno M, Haucke V, Dirksen RT, Dowling JJ. Tamoxifen therapy in a murine model of myotubular myopathy. Nat Commun. 2018 Nov 19;9(1):4849. doi: 10.1038/s41467-018-07057-5. PubMed 30451841 ↗
  • Gayi E, Neff LA, Massana Munoz X, Ismail HM, Sierra M, Mercier T, Decosterd LA, Laporte J, Cowling BS, Dorchies OM, Scapozza L. Tamoxifen prolongs survival and alleviates symptoms in mice with fatal X-linked myotubular myopathy. Nat Commun. 2018 Nov 19;9(1):4848. doi: 10.1038/s41467-018-07058-4. PubMed 30451843 ↗

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04915846
Lead sponsor
James Dowling
Collaborators
Canadian Institutes of Health Research (CIHR), Cures Within Reach, The Joshua Frase Foundation USA, Will Cure USA, Mogford Campbell Family Chair Fund, Myotubular Trust, Great Ormond Street Hospital Charity, Sparks
Responsible party
James Dowling (Staff clinician and senior scientist, The Hospital for Sick Children) — Sponsor-investigator
First posted
Jun 7, 2021
Start date
Dec 18, 2020
Primary completion
May 9, 2024
Completion
May 9, 2024
Last update
Sep 19, 2024

Study contacts

Jame J Dowling, MD, PhD
principal investigator · The Hospital for Sick Children

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is terminated, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.

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