The effect of wearing night splints for one year on the standing motor function of patients with Duchenne muscular dystrophy

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

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Measurements of Motor Function and Other Clinical Outcome Parameters in Ambulant Children with Duchenne Muscular Dystrophy

Journal of Visualized Experiments ◽

10.3791/58784 ◽

2019 ◽

Cited By ~ 1

Author(s):

Sara Nagy ◽

Simone Schmidt ◽

Patricia Hafner ◽

Andrea Klein ◽

Daniela Rubino-Nacht ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Clinical Outcome ◽

Motor Function ◽

Outcome Parameters

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Use of a wearable device to assess sleep and motor function in Duchenne muscular dystrophy

Muscle & Nerve ◽

10.1002/mus.26759 ◽

2019 ◽

Vol 61 (2) ◽

pp. 198-204 ◽

Cited By ~ 1

Author(s):

Benjamin I. Siegel ◽

Ayse Cakmak ◽

Erik Reinertsen ◽

Macarthur Benoit ◽

Janet Figueroa ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Function ◽

Wearable Device

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Duchenne Muscular Dystrophy: Canadian Paediatric Neuromuscular Physicians Survey

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100009926 ◽

2010 ◽

Vol 37 (2) ◽

pp. 195-205 ◽

Cited By ~ 16

Author(s):

Hugh J. McMillan ◽

Craig Campbell ◽

Jean K. Mah

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Vitamin D Supplementation ◽

Cardiac Complications ◽

Multidisciplinary Teams ◽

Health Maintenance ◽

Routine Surveillance ◽

Independent Ambulation ◽

Recommended Guidelines ◽

Night Splints

Background:Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood.Method:To assess the current care of paediatric DMD patients in Canada, a questionnaire was mailed to 17 physicians who were members of the Canadian paediatric neuromuscular group. Areas of enquiry included; 1) multidisciplinary team composition; 2) means of DMD diagnosis; 3) corticosteroid use; surveillance and management for: 4) orthopaedic, 5) respiratory and 6) cardiac complications and 7) health maintenance (nutrition & immunizations).Results:Completed surveys were returned by 14/17 (82%) of physicians. Twelve respondents followed DMD patients. All centres had multidisciplinary teams, including respirology (11/12), child neurology or physiatry (11), physiotherapy (9), occupational therapy (9) and orthopaedic surgery (7). Deflazacort 0.9mg/kg/d was used at all centres, which was continued after loss of independent ambulation (11), along with routine calcium and vitamin D supplementation (10). Night splints were prescribed at all centres. Routine surveillance studies included pulmonary function testing (11), sleep studies (10), EKG/echocardiogram (10), bone density (DEXA) scans (10), spine radiography (9), and dietician referral (4).Conclusion:Paediatric DMD patients are receiving relatively consistent care in multidisciplinary clinics across Canada, in accordance with recommended guidelines for DMD.

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Timed function tests, motor function measure, and quantitative thigh muscle MRI in ambulant children with Duchenne muscular dystrophy: A cross-sectional analysis

Neuromuscular Disorders ◽

10.1016/j.nmd.2017.10.003 ◽

2018 ◽

Vol 28 (1) ◽

pp. 16-23 ◽

Cited By ~ 8

Author(s):

Simone Schmidt ◽

Patricia Hafner ◽

Andrea Klein ◽

Daniela Rubino-Nacht ◽

Vanya Gocheva ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Function ◽

Thigh Muscle ◽

Muscle Mri ◽

Cross Sectional ◽

Cross Sectional Analysis ◽

Function Tests ◽

Sectional Analysis ◽

Function Measure

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Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial

10.21203/rs.2.10085/v1 ◽

2019 ◽

Author(s):

Sara Nagy ◽

Patricia Hafner ◽

Simone Schmidt ◽

Daniela Rubino-Nacht ◽

Sabine Schädelin ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Function ◽

Open Label ◽

Phase 3 ◽

Double Blind ◽

Safety And Efficacy ◽

Open Label Extension ◽

To Receive ◽

Function Measure

Abstract BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocorticoids with numerous long-term side effects. Tamoxifen is a selective estrogen receptor regulator, and shows besides its antitumor activity also antioxidant actions and regulatory roles in the calcium homeostasis. In a mouse model of DMD, oral tamoxifen significantly improved muscle strength and reduced muscle fatigue. This multicenter, randomized, double-blind, placebo controlled phase 3 trial aims to demonstrate safety and efficacy of tamoxifen over placebo in pediatric patients with DMD. After completion of the double-blind phase, an open label extension of the study will be offered to all participants. METHODS/DESIGN At least 71 ambulant and up to 20 non-ambulant patients with DMD are planned to be enrolled at multiple European sites. Patients will be randomly assigned to receive either tamoxifen 20mg or placebo daily over 48 weeks. In the open-label extension phase, all patients will be offered to receive tamoxifen for further 48 weeks. The primary endpoint of the double-blind phase is defined as the change of the D1 domain of the motor function measure in ambulant patients or a change of the D2 domain in non-ambulant patients under tamoxifen compared to placebo. Secondary outcome measures include change in timed function tests, quantitative muscle testing, and quantitative MRI of thigh muscles. Laboratory analyses including biomarkers of tamoxifen metabolism and muscle dystrophy will also be assessed. DISCUSSION The aim of the study is to investigate whether tamoxifen can reduce disease progression in ambulant and non-ambulant DMD patients over 48 weeks. Motor function measure comprises the primary endpoint, whereas further clinical and radiological assessments and laboratory biomarkers are performed to provide more data on safety and efficacy. An adjacent open label extension phase is planned to test if earlier initiation of the treatment with tamoxifen (verum arm of double blind phase) compared to a delayed start can reduce disease progression more efficiently.

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Tamoxifen in Duchenne muscular dystrophy (TAMDMD): study protocol for a multicenter, randomized, placebo-controlled, double-blind phase 3 trial

10.21203/rs.2.10085/v2 ◽

2019 ◽

Author(s):

Sara Nagy ◽

Patricia Hafner ◽

Simone Schmidt ◽

Daniela Rubino-Nacht ◽

Sabine Schädelin ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Motor Function ◽

Open Label ◽

Phase 3 ◽

Double Blind ◽

Safety And Efficacy ◽

Open Label Extension ◽

To Receive ◽

Function Measure

Abstract BACKGROUND Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder of childhood with a devastating disease course. Several targeted gene therapies and molecular approaches have been or are currently tested in clinical trials; however, a causative therapy is still not available and best supportive care is limited to oral glucocorticoids with numerous long-term side effects. Tamoxifen is a selective estrogen receptor regulator, and shows besides its antitumor activity also antioxidant actions and regulatory roles in the calcium homeostasis. In a mouse model of DMD, oral tamoxifen significantly improved muscle strength and reduced muscle fatigue. This multicenter, randomized, double-blind, placebo controlled phase 3 trial aims to demonstrate safety and efficacy of tamoxifen over placebo in pediatric patients with DMD. After completion of the double-blind phase, an open label extension of the study will be offered to all participants. METHODS/DESIGN At least 71 ambulant and up to 20 non-ambulant patients with DMD are planned to be enrolled at multiple European sites. Patients will be randomly assigned to receive either tamoxifen 20mg or placebo daily over 48 weeks. In the open-label extension phase, all patients will be offered to receive tamoxifen for further 48 weeks. The primary endpoint of the double-blind phase is defined as the change of the D1 domain of the motor function measure in ambulant patients or a change of the D2 domain in non-ambulant patients under tamoxifen compared to placebo. Secondary outcome measures include change in timed function tests, quantitative muscle testing, and quantitative MRI of thigh muscles. Laboratory analyses including biomarkers of tamoxifen metabolism and muscle dystrophy will also be assessed. DISCUSSION The aim of the study is to investigate whether tamoxifen can reduce disease progression in ambulant and non-ambulant DMD patients over 48 weeks. Motor function measure comprises the primary endpoint, whereas further clinical and radiological assessments and laboratory biomarkers are performed to provide more data on safety and efficacy. An adjacent open label extension phase is planned to test if earlier initiation of the treatment with tamoxifen (verum arm of double blind phase) compared to a delayed start can reduce disease progression more efficiently.

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