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Trial record 28 of 70 for:    /kg | "muscular dystrophy, duchenne and becker types"

Tamoxifen in Duchenne Muscular Dystrophy (TAMDMD)

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ClinicalTrials.gov Identifier: NCT03354039
Recruitment Status : Recruiting
First Posted : November 27, 2017
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Brief Summary:
A randomised, double blind, placebo controlled, 48-week clinical trial with a core population (group A) of 79 ambulant 6.5 to 12 years old Duchenne's muscular dystrophy (DMD) patients that are under stable standard treatment of care with glucocorticoids. Furthermore, the investigators plan to include 16-20 non-ambulant patients who do not receive glucocorticoids (as parallel group B), 10 to 16 years old, to obtain efficacy and safety data in a broader DMD population. All patients will receive 20 mg of tamoxifen (TAM) or placebo once daily during 48 weeks.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Tamoxifen Drug: Matching placebo Phase 3

Detailed Description:

This is a 48-week multicentre, parallel, randomised, double-blind, placebo controlled phase 3 safety and efficacy trial. There are two treatment arms: Tamoxifen (verum) and placebo (control), with treatment allocation of 1:1.

The investigators plan to screen at least 79 and to enroll at least 71 ambulant DMD patients aged between 6.5 and 12 years (group A) and 16 - 20 non-ambulant DMD patients aged between 10 and 16 years (group B). In order to reach statistical power, 60 ambulant patients (group A) need to complete the trial. Treatment with 20 mg Tamoxifen once daily will be given for the total trial duration of 48 weeks.

Only patients with glucocorticoids (standard treatment of care) will be included in group A (ambulant patients) and only non-glucocorticoid users in group B. At baseline as well as at the end of the study clinical, laboratory, and MRI measurements will be performed. These include the Motor Function Measure (MFM) scale, timed function tests, the 6 minute walking distance, quantitative muscle testing (QMT) and quantitative thigh muscle MRI, questionnaires. A physical examination, an ECG, vital signs as well as safety laboratory blood analyses will be performed at every visit. Furthermore, an x-ray of the hand and a dual energy x-ray absorptiometry (DEXA)-scan will be performed at baseline and at the end of the study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tamoxifen in Duchenne Muscular Dystrophy: A Multicenter, Randomised, Double-blind, Placebo-controlled, Phase 3 Safety and Efficacy 48-week Trial
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Tamoxifen 20 mg once daily
DMD patients randomised to verum will receive 20 mg (0.6mg/kg) of TAM daily.
Drug: Tamoxifen
DMD patients randomised to verum will receive 20 mg (0.6mg/kg) of Tamoxifen daily. Treatment will be given for the total period of 48 weeks.

Placebo Comparator: Matching placebo once daily
Patients randomised to placebo will be administered matching placebo.
Drug: Matching placebo
Patients randomised to placebo will be administered matching placebo. Treatment will be given for the total period of 48 weeks.




Primary Outcome Measures :
  1. Reduction of disease progression [ Time Frame: Baseline to week 48 ]
    To test if tamoxifen treatment, compared to placebo, reduces the progression of the disease in 6.5-12 years old ambulant DMD patients (Group A) by at least 50% (using the MFM D1 subscore as primary clinical endpoint).


Secondary Outcome Measures :
  1. Muscle function measured by D2 MFM subscore [ Time Frame: Baseline to week 48 ]
    D2 MFM subscore from baseline to week 48 under TAM treatment compared to placebo.

  2. Muscle function measured by D3 MFM subscore [ Time Frame: Baseline to week 48 ]
    D3 MFM subscore from baseline to week 48 under TAM treatment compared to placebo.

  3. Muscle function measured by North Star Ambulatory Assessment [ Time Frame: Baseline to week 48 ]
    North Star Ambulatory Assessment from baseline to week 48 under TAM treatment compared to placebo.

  4. Muscle function measured by proximal upper limb function [ Time Frame: Baseline to week 48 ]
    Proximal upper limb function from baseline to week 48 under TAM treatment compared to placebo.

  5. Muscle function measured by 6 minute walking distance in meter [ Time Frame: Baseline to week 48 ]
    6 minute walking distance in meter from baseline to week 48 under TAM treatment compared to placebo.

  6. Muscle function measured by 10 meter walking time in seconds [ Time Frame: Baseline to week 48 ]
    10 meter walking time in seconds from baseline to week 48 under TAM treatment compared to placebo.

  7. Muscle function measured by time to rise from lying on the floor / supine up in seconds [ Time Frame: Baseline to week 48 ]
    time to rise from lying on the floor / supine up in seconds from baseline to week 48 under TAM treatment compared to placebo.

  8. Muscle force measured by quantitative muscle testing (using Myogrip) [ Time Frame: Baseline to week 48 ]
    Quantitative muscle testing (using Myogrip) from baseline to week 48 under TAM treatment compared to placebo.

  9. Muscle Degeneration measured by MRI [ Time Frame: Baseline to week 48 ]
    Quantitative muscle MRI including muscle fat fraction (MFF) and T2 times of thigh muscles visualised by MRI from baseline to week 48 under TAM treatment compared to placebo.


Other Outcome Measures:
  1. Patient reported outcome measured by PARS III questionnaire [ Time Frame: Baseline to week 48 ]
    Personal Adjustment and Role Skills Scale (PARS-III) from baseline to week 48 under TAM treatment under TAM treatment compared to placebo.



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Ages Eligible for Study:   78 Months to 16 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Group A (ambulant patients)

  • Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining
  • Stable treatment with glucocorticoids >6 months (no significant change in dosage (>0.2mg/kg)) at screening; dosing adaptations according to weight change are allowed
  • Male gender
  • 6.5 to 12 years of age at time of screening
  • weight >15kg
  • ambulant patients
  • able to walk at least 350 meters in 6 minute walking distance test without assistance
  • MFM D1 subdomain of the MFM scale >40% at screening
  • Ability to provide informed consent and to comply with study requirements

Group B (non-ambulant patients)

  • Documented diagnosis of DMD by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining
  • Not using glucocorticoids for >6 months
  • Male gender
  • Non-ambulant patients (walking distance less than 10 meters)
  • 10 to 16 years of age at time of screening
  • Ability to provide informed consent and to comply with study requirements

Exclusion Criteria:

  • Known individual hypersensitivity or allergy to tamoxifen
  • Female gender
  • Use of tamoxifen or testosterone within the last 3 months
  • Known or suspected malignancy
  • Other chronic disease or clinically relevant limitation of renal, liver or heart function
  • Known or suspected non-compliance
  • Any injury which may impact functional testing, e.g. upper or lower limb fracture
  • Planned or expected spinal fusion surgery during the study period (as judged by the Investigator; i.e. due to rapid progressing scoliosis), previous spinal fusion surgery is allowed if it took place more than 6 months prior to screening.
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders of the participant/parents (as judged by the investigator)
  • Concomitant participation in any other interventional trial (and up to 3 months prior to screening)

Group A:

  • Glucocorticoid naïve patients
  • Start of glucocorticoid treatment or change in dosage <6 month prior to screening (dosing adaptations according to weight change are allowed)

Group B:

  • Glucocorticoid treated patients or patients that stopped glucocorticoid treatment <6 month prior to screening
  • Assisted ventilation of any kind necessary

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03354039


Contacts
Contact: Dirk Fischer, MD +41 61 704 12 12 admin-tamdmd@ukbb.ch
Contact: Patricia Hafner, MD +41 61 704 12 12 admin-tamdmd@ukbb.ch

Locations
Switzerland
University Children's Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Patricia Hafner, MD    +41 61 704 12 12    patricia.hafner@ukbb.ch   
Contact: Daniela Rubino    +41 61 704 12 12    daniela.rubino-nacht@ukbb.ch   
Principal Investigator: Dirk Fischer, MD         
Sub-Investigator: Patricia Hafner, MD         
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Dirk Fischer, MD University Children's Hospital Basel

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03354039     History of Changes
Other Study ID Numbers: TAMDMD
First Posted: November 27, 2017    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by University Hospital, Basel, Switzerland:
DMD

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Tamoxifen
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents