Clinical trial NCT00313677: Clinical Trial Readiness for the Dystroglycanopathies
Official title: Clinical Trial Readiness for the Dystroglycanopathies
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Muscular Dystrophy
Keywords: muscular dystrophy
MD
fukutin-related protein gene
limb girdle
FKRP gene
congenital muscular dystrophy
childhood onset LGMD
adult onset LGMD
POMT1
POMT2
POMGnT1
LARGE
alpha dystroglycan
dystroglycanopathy
ISPD/CRPPA
DPM 1, 2 or 3
GMPPB
B3GNT1/B4GAT1
B3GALNT2
GTDC2/POMGnT2
TMEM5/RXYLT1
Fukutin
DAG1
POMK/SGK196
DOLK
GO5R2
TRAPPC11
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2006-04-12
Enrollment: 190
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: neuromuscular care clinic

Brief summary: The purpose of the study is to describe the early signs and symptoms of the dystroglycanopathies, and to gather information that will be required for future clinical trials.

Detailed description: Muscular dystrophies are a diverse group of inherited disorders characterized by progressive muscle weakness and wasting. The disorders are caused by mutations, or changes, in genes. Genes are tiny pieces of inherited material (DNA) that direct the body to make certain kinds of proteins.

In this study, researchers will examine the clinical presentation of muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan. Patients with dystroglycanopathies could have mutations in any one of the more than 20 currently identified genes, or evidence of dystroglycanopathy in biopsied muscle tissue . Symptoms range from congenital muscular dystrophy that may involve the brain and eye, through an adult-onset limb girdle muscular dystrophy.

The study involves a clinical evaluation at the University of Iowa. The evaluation includes muscle strength and motor ability testing, lung function testing, quality of life and activity assessment, and a review of past medical history. Portions of this evaluation will be repeated on a yearly basis. Financial assistance is available for travel to Iowa City. Support is also available for genetic testing for people with a dystroglycanopathy diagnosis based on muscle or skin biopsy analysis.

Knowledge gained from this study will improve healthcare recommendations for people with dystroglycanopathies, and provide a baseline for further study, including potential treatment options.

Eligibility criteria: Inclusion Criteria:

* Elevated CK (creatine kinase)
* Evidence of a dystroglycanopathy as determined by review of muscle pathology OR documented mutation in one of the known genes OR abnormal alpha-dystroglycan glycosylation in cultured fibroblasts
* Dystroglycanopathies are predicted to affect all racial and ethnic backgrounds, and all patients with dystroglycanopathies will be eligible for participation.
* Participants may be of any age, including children, and males and females will be recruited equally.
* Patients will have varying degrees of muscular weakness, but otherwise should be in relatively good health.

Exclusion Criteria:

* There are no exclusion criteria.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa, 200 Hawkins Drive
state: Iowa
Study officials:
affiliation: University of Iowa
name: Katherine Mathews, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Co-Investigator
name: Kevin Campbell, Ph.D.
role: STUDY_DIRECTOR
affiliation: Co-Investigator
name: Steven A. Moore, M.D. Ph.D.
role: STUDY_DIRECTOR
References:
citation: Coffey LN, Stephan CM, Zimmerman MB, Decker CK, Mathews KD. Diagnostic delay in patients with FKRP-related muscular dystrophy. Neuromuscul Disord. 2021 Dec;31(12):1235-1240. doi: 10.1016/j.nmd.2021.08.013. Epub 2021 Sep 6.
citation: Libell EM, Bowdler NC, Stephan CM, Zimmerman MB, Gedlinske AM, Mathews KD. The outcomes and experience of pregnancy in limb girdle muscular dystrophy type R9. Muscle Nerve. 2021 Jun;63(6):812-817. doi: 10.1002/mus.27184. Epub 2021 Feb 10.
citation: Gedlinske AM, Stephan CM, Mockler SRH, Laubscher KM, Laubenthal KS, Crockett CD, Zimmerman MB, Mathews KD. Motor outcome measures in patients with FKRP mutations: A longitudinal follow-up. Neurology. 2020 Oct 13;95(15):e2131-e2139. doi: 10.1212/WNL.0000000000010604. Epub 2020 Aug 6.
citation: Carlson CR, McGaughey SD, Eskuri JM, Stephan CM, Zimmerman MB, Mathews KD. Illness-associated muscle weakness in dystroglycanopathies. Neurology. 2017 Dec 5;89(23):2374-2380. doi: 10.1212/WNL.0000000000004720. Epub 2017 Nov 3.
citation: Crockett CD, Bertrand LA, Cooper CS, Rahhal RM, Liu K, Zimmerman MB, Moore SA, Mathews KD. Urologic and gastrointestinal symptoms in the dystroglycanopathies. Neurology. 2015 Feb 3;84(5):532-9. doi: 10.1212/WNL.0000000000001213. Epub 2015 Jan 7.