Historically Controlled Trial of Corticosteroids in Young Boys With Duchenne Muscular Dystrophy

NCT ID: NCT02167217

Last Updated: 2018-12-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-17

Study Completion Date

2017-03-22

Brief Summary

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While it has been known for many years that corticosteroid use benefits boys with Duchenne Muscular dystrophy (DMD), most clinicians do not consider treating until after age 3 or 4 years of age. The primary reason for the delay is that daily corticosteroid use has many side effects including short stature, obesity, and osteoporosis. A recent randomized blinded study of weekend oral corticosteroid use over one year showed equal improvement in strength with fewer side effects, particularly as related to growth and cushingoid changes. The investigators will test the efficacy of oral weekend corticosteroid use in infants and young boys with DMD who are under age 30 months. The investigators have demonstrated that the Bayley-III Scales of Infant development shows that infants and young boys in this age group who are untreated decline in abilities when compared to their peers. Here, in this Phase 2 historically controlled trial, the investigators will use these two measures and treat boys at five Muscular Dystrophy Association-DMD centers

Detailed Description

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Objective. Determine if twice-weekly high dose oral prednisone improves gross motor development in infants and young boys with DMD. The investigators will perform a phase 2 historically controlled trial of oral twice-weekly prednisone (5mg/kg/dose on two consecutive days) in infants and young boys with DMD. Here the investigators propose to study the effect of this therapy in a multicenter trial of boys with DMD who are less than 30 months old at the baseline visit. Each boy will be followed for one year.

Aim 1. Determine if treatment improves gross motor function in infants with DMD over a 6-12-month period as measured by the Bayley-III. The Bayley-III infant score is the primary motor clinical endpoint of this therapeutic trial. Secondary outcomes include fine motor function, speech and language, and social function.

Aim 2. Determine if treatment improves the Adaptive Behavior Subtest of the Bayley-III (ABS) as scored by the infants' primary caregiver. In the study of untreated boys, the primary caregiver noted clear deficits, predominantly related to areas relevant to gross motor function. The ABS Aim 3. Determine if treatment improves performance on the North Star Ambulatory Assessment (NSAA) for those boys who are ambulatory.

Aim 4. Determine if treatment with weekly corticosteroids is tolerated and is safe in boys with DMD who are less than 30 months of age.

Objective 2. Determine if ultrasound of biceps and quadriceps using calibrated backscatter improves in infants and young boys with DMD who are treated with oral high dose weekly corticosteroids. Preliminary data of ultrasound imaging in infants and young boys with DMD demonstrate progressive structural damage as measured by calibrated backscatter. The ultrasound studies will be limited to the infants and boys who will enroll at the primary site (Washington University) where Dr. Craig Zaidman has the equipment and expertise to accomplish this aim.

Objective 3. Determine if caregiver burden changes with treatment of infants and young boys with DMD. Preliminary data from questionnaires suggests the caregiver burden for the primary caregiver of untreated infant and young boys with DMD is minimal. Assessment of this with in this trial will allow us to discern if this changes with a therapeutic trial.

Conditions

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Duchenne Muscular Dystrophy

Keywords

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Duchenne Muscular Dystrophy Corticosteroids Infants Young Children Toddlers

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oral Prednisolone

Oral Prednisolone 5mg/kg/ day on two consecutive days, Friday and Saturday with breakfast

Group Type EXPERIMENTAL

Prednisolone

Intervention Type DRUG

Prednisolone (5mg per kg) will be taken on two consecutive days, Friday and Saturday mornings each week with breakfast

Interventions

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Prednisolone

Prednisolone (5mg per kg) will be taken on two consecutive days, Friday and Saturday mornings each week with breakfast

Intervention Type DRUG

Other Intervention Names

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prednisolone (Morton Grove Pharm.) National Drug Code is 60432-212-08

Eligibility Criteria

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Inclusion Criteria

1. Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal, and genetic mutation known to be causative for Duchenne muscular dystrophy .
2. Appropriate degree of weakness for age, creatine kinase greater than 20 times the upper limit of normal and genetic or biopsy confirmation of Duchenne muscular dystrophy in a primary relative (e.g. brother or maternal uncle).
3. De-identified, genetic studies will be reviewed by collaborator Kevin Flanigan, MD prior to enrollment of subjects.
4. Age at entry: one month through 30 months.

Exclusion Criteria

* Prior treatment with corticosteroids
Minimum Eligible Age

1 Month

Maximum Eligible Age

30 Months

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Nationwide Children's Hospital

OTHER

Sponsor Role collaborator

Northwestern University Feinberg School of Medicine

OTHER

Sponsor Role collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role collaborator

University of California, Davis

OTHER

Sponsor Role collaborator

Nemours Children's Hospital

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anne M Connolly, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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University of California Davis

Sacramento, California, United States

Site Status

Nemours Hospital

Orlando, Florida, United States

Site Status

Laurie Children's Hospital Of Chicago

Chicago, Illinois, United States

Site Status

Washington University in Saint Louis

St Louis, Missouri, United States

Site Status

Research Institute Center for Gene Therapy at Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

University of Texas South Western Medical Center of Dallas

Dallas, Texas, United States

Site Status

Countries

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United States

References

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Connolly AM, Florence JM, Cradock MM, Malkus EC, Schierbecker JR, Siener CA, Wulf CO, Anand P, Golumbek PT, Zaidman CM, Philip Miller J, Lowes LP, Alfano LN, Viollet-Callendret L, Flanigan KM, Mendell JR, McDonald CM, Goude E, Johnson L, Nicorici A, Karachunski PI, Day JW, Dalton JC, Farber JM, Buser KK, Darras BT, Kang PB, Riley SO, Shriber E, Parad R, Bushby K, Eagle M; MDA DMD Clinical Research Network. Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network. Neuromuscul Disord. 2013 Jul;23(7):529-39. doi: 10.1016/j.nmd.2013.04.005. Epub 2013 May 28.

Reference Type BACKGROUND
PMID: 23726376 (View on PubMed)

Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Dec;12(10):917-25. doi: 10.1016/s0960-8966(02)00180-3.

Reference Type BACKGROUND
PMID: 12467746 (View on PubMed)

Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, Kornberg AJ, Bertorini TE, Nevo Y, Lotze T, Pestronk A, Ryan MM, Monasterio E, Day JW, Zimmerman A, Arrieta A, Henricson E, Mayhew J, Florence J, Hu F, Connolly AM. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011 Aug 2;77(5):444-52. doi: 10.1212/WNL.0b013e318227b164. Epub 2011 Jul 13.

Reference Type BACKGROUND
PMID: 21753160 (View on PubMed)

Connolly AM, Zaidman CM, Golumbek PT, Cradock MM, Flanigan KM, Kuntz NL, Finkel RS, McDonald CM, Iannaccone ST, Anand P, Siener CA, Florence JM, Lowes LP, Alfano LN, Johnson LB, Nicorici A, Nelson LL, Mendell JR; MDA DMD Clinical Research Network. Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy. Muscle Nerve. 2019 Jun;59(6):650-657. doi: 10.1002/mus.26441. Epub 2019 Feb 23.

Reference Type DERIVED
PMID: 30706490 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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201308062

Identifier Type: -

Identifier Source: org_study_id