Clinical trial NCT01417533: A Natural History Study of Patients With GNE Myopathy and GNE-Related Diseases
Official title: A Natural History Study of Patients With GNE Myopathy and GNE-Related Diseases
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: GNE Myopathy
GNE Related Diseases
Keywords: Hereditary Inclusion Body Myopathy
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: Therapeutics for Rare and Neglected Diseases (TRND)
First posted: 2011-08-16
Enrollment: 125
Sex: ALL
Minimum age (years): 4
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of GNE myopathy or GNE-related disease. Subjects that are a carrier family member or a caregiver of a patient on the study are eligible to participate.

Brief summary: Background:

- GNE Myopathy is a disease that causes walking difficulties and increasing muscle weakness. It usually develops in young adults (between 20 and 30 years of age), and affects arm and leg muscles. HIBM is caused by mutations in a gene that may affect how the muscles function. Researchers want to learn more about the causes, symptoms, and effects of HIBM.

Objectives:

- To collect genetic and medical information from people with GNE Myopathy .

Eligibility:

- Individuals between 18 and 80 years of age who have GNE Myopathy and do not use a wheelchair. - Participants must be willing to stop any current treatment of HIBM while enrolled in the study.

Design:

* Participants will be screened with a medical history, physical exam, and neurological exam.
* At the first visit, participants will have the following tests:
* Questionnaires about the impact of HIBM on daily activities, mood, and quality of life
* 24-hour urine collection
* Blood samples
* Heart function tests
* Muscle strength and endurance tests, including walking
* Imaging study of the muscles
* Participants will return for followup visits at 6, 12, and 18 months. They may be asked to return for a final visit at 24 months. Not all tests will be performed at each visit.
* Treatment will not be provided as part of this protocol.

For more information, visit our website: http://hibmstudy.nhgri.nih.gov/

Detailed description: This is a prospective observational study to evaluate patients with GNE myopathy and other GNE-related diseases. The GNE gene encodes for UDP-GlcNAc 2-epimerase/ManNAc kinase, the bifunctional enzyme that initiates and regulates intracellular sialic acid (Neu5Ac) biosynthesis and glycan sialylation. GNE myopathy is a rare, autosomal recessive myopathy with onset in early adulthood characterized by progressive skeletal muscle atrophy and weakness. The impairment of Neu5Ac production is presumed to cause decreased sialylation of muscle glycoproteins, resulting in muscle deterioration. Other GNE-related diseases such as congenital thrombocytopenia have been recently identified, but the pathophysiology is not well understood. In this protocol, we plan to evaluate patients with GNE myopathy and other GNE-related diseases clinically, biochemically, and molecularly to characterize the mechanisms of disease, to delineate the natural history, phenotypes, progression and complications of GNE-related diseases, and to identify endpoints and biomarkers to support clinical trials testing potential therapies.

Eligibility criteria: * INCLUSION CRITERIA:

  1. Age 4-80 years, either gender, inclusive.
  2. Diagnosis of GNE myopathy or GNE-related diseases based upon the identification of GNE gene mutations. Molecular confirmation of the diagnosis will be obtained for all subjects in the study.
  3. Subjects that are a carrier family member of a patient on the study are eligible to participate.
  4. Must be able to provide informed consent.

EXCLUSION CRITERIA:

1. Psychiatric illness or other diseases that would interfere with the subject s ability to comply with the requirements of this protocol.
2. Hepatic laboratory parameters (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\]) or renal laboratory parameters (creatinine, blood urea nitrogen \[BUN\]) greater than 3 times the upper limit of normal.
3. Presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease not related to the primary disease process.

Primary outcomes:
measure: Natural History
timeFrame: Ongiong
Secondary outcomes:
measure: Endpoints
timeFrame: Ongoing
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Human Genome Research Institute (NHGRI)
name: Francis Rossignol, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu CY, Yao J, Kovacs WC, Shrader JA, Joe G, Ouwerkerk R, Mankodi AK, Gahl WA, Summers RM, Carrillo N. Skeletal Muscle Magnetic Resonance Biomarkers in GNE Myopathy. Neurology. 2021 Feb 2;96(5):e798-e808. doi: 10.1212/WNL.0000000000011231. Epub 2020 Nov 20.