A Natural History Study of Patients With GNE Myopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01417533
Recruitment Status : Recruiting
First Posted : August 16, 2011
Last Update Posted : January 18, 2019
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) )

Brief Summary:


- 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.


- To collect genetic and medical information from people with hereditary inclusion body myopathy.


- 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.


  • 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.

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Condition or disease
Hereditary Inclusion Body Myopathy

Detailed Description:
GNE myopathy, previously known as Hereditary Inclusion Body Myopathy (HIBM), or Nonaka Myopathy, is an autosomal recessive myopathy with onset in early adulthood characterized by progressive muscle atrophy and weakness. The causative gene, GNE, encodes for the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) that catalyzes the rate-limiting step in the biosynthesis of sialic acid (Neu5Ac). The subsequent impairment of Neu5Ac production is presumed to cause decreased sialylation of GNE myopathy muscle glycoproteins, resulting in muscle deterioration. In this protocol, we will clinically evaluate patients with GNE myopathy. 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 phenotype, progression and complications of the disease. Additionally, the study is designed to identify endpoints and biomarkers for future therapeutic trials

Study Type : Observational
Estimated Enrollment : 100 participants
Time Perspective: Prospective
Official Title: A Natural History Study of Patients With GNE Myopathy
Study Start Date : August 13, 2011

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. The functional outcome measures (potential endpoints) to be used to test future therapeutic interventions. [ Time Frame: 0, 6, 12, 18, and possibly 24 months ]
  2. 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 ]
  3. The rates of progression for individual subjects. [ Time Frame: 0, 6, 12, 18, and possibly 24 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    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.


  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01417533

Contact: John R Perreault, C.R.N.P. (301) 827-9235
Contact: Nuria Carrillo, M.D. (301) 402-2324

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 Office of Patient Recruitment (OPR)    800-441-1222 ext TTY8864111010   
Sponsors and Collaborators
National Human Genome Research Institute (NHGRI)
Therapeutics for Rare and Neglected Diseases (TRND)
Principal Investigator: Nuria Carrillo, M.D. National Human Genome Research Institute (NHGRI)

Additional Information:
Responsible Party: National Human Genome Research Institute (NHGRI) Identifier: NCT01417533     History of Changes
Other Study ID Numbers: 110218
First Posted: August 16, 2011    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: April 12, 2018

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

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