Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Natural History Study of Patients With GNE Myopathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Therapeutics for Rare and Neglected Diseases (TRND)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
ClinicalTrials.gov Identifier:
NCT01417533
First received: August 13, 2011
Last updated: September 27, 2016
Last verified: September 2016
  Purpose

Background:

- Hereditary inclusion body myopathy (HIBM) 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 hereditary inclusion body myopathy.

Eligibility:

- Individuals between 18 and 80 years of age who have hereditary inclusion body 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/


Condition
Hereditary Inclusion Body Myopathy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Natural History Study of Patients With GNE Myopathy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • The baseline rate of progression of complications and its correlation with age of onset of the disease. [ Time Frame: 0, 6, 12, 18, and possibly 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The functional outcome measures (potential endpoints) to be used to test future therapeutic interventions. [ Time Frame: 0, 6, 12, 18, and possibly 24 months ] [ Designated as safety issue: No ]
  • The identification of potential serum biomarkers (sialylated as disease markers and the correlation between muscle magnetic resonance imaging (MRI) findings with progression of the disease [ Time Frame: 0, 6, 12, 18, and possibly 24 months ] [ Designated as safety issue: No ]
  • The rates of progression for individual subjects. [ Time Frame: 0, 6, 12, 18, and possibly 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: July 2011
Detailed Description:
GNE myopathy, also known as Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive myopathy with onset in early adulthood characterized by progressive muscle weakness. The causative gene, GNE, codes for the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) that catalyzes the first two steps in the biosynthesis of sialic acid (SA). The subsequent paucity of SA production is presumed to cause decreased sialylation of GNE myopathy muscle glycoproteins, resulting in muscle deterioration. To date, the amount of prospectively collected and published natural history data on GNE myopathy has been minimal due to the rare nature of this disease. This natural history study seeks to further characterize the rate of progression of the disease and how it relates to age of onset. Additionally, the study is designed to elucidate functional outcome measures (endpoints) for future therapeutic trials, and correlate serum biomarkers and muscle magnetic resonance imaging (MRI) findings to progression of the disease.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age 18-80 years, either gender, inclusive.
    2. Diagnosis of GNE myopathy based upon:

      1. Consistent clinical course, family history of GNE myopathy or characteristic findings on muscle biopsy, and
      2. Identification of two GNE gene mutations. Molecular confirmation of the diagnosis will be obtained for all subjects in the study.
    3. Subjects may be taking ManNAc at the time of their enrollment, but must be willing to stop treatment with ManNAc, sialic acid (SA), intravenous immunoglobulin (IVIG), and/or other supplements containing SA (e.g., St John s wort, sialyllactose) after the screening assessment and must be willing to remain off treatment for the duration of the study.
    4. Ability to travel to the NIH Clinical Center repeatedly for admissions.
    5. Subjects that are a carrier family member or a caregiver of a patient on the study are eligible to participate.
    6. Must be able to provide informed consent.

EXCLUSION CRITERIA:

  1. Inability to travel to the NIH Clinical Center for repeated evaluations.
  2. Psychiatric illness or other diseases that would interfere with the subject s ability to comply with the requirements of this protocol.
  3. Hepatic laboratory parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-GTP) or renal laboratory parameters (creatinine, blood urea nitrogen [BUN]) greater than 3 times the upper limit of normal.
  4. Presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease not related to the primary disease process.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01417533

Contacts
Contact: John R Perreault, C.R.N.P. (301) 827-9235 john.perreault@nih.gov
Contact: Nuria Carrillo-Carrasco, M.D. (301) 402-2324 carrilln@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-441-1222 ext TTY8864111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Therapeutics for Rare and Neglected Diseases (TRND)
Investigators
Principal Investigator: Nuria Carrillo-Carrasco, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
Responsible Party: National Human Genome Research Institute (NHGRI)
ClinicalTrials.gov Identifier: NCT01417533     History of Changes
Other Study ID Numbers: 110218  11-HG-0218 
Study First Received: August 13, 2011
Last Updated: September 27, 2016
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Hereditary Inclusion Body Myopathy
N-Acetyl-D-mannosamine (ManNAc)
UDP-N-acetyglucosamine 2-epimerase (GNE)
Sialic Acid
Muscular Dystrophy
HIBM

Additional relevant MeSH terms:
Muscular Diseases
Distal Myopathies
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Muscular Dystrophies
Muscular Disorders, Atrophic
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on December 08, 2016