A Natural History Study of Patients With Hereditary Inclusion Body Myopathy

This study is currently recruiting participants.
Verified May 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01417533
First received: August 13, 2011
Last updated: March 14, 2014
Last verified: May 2013
  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 Hereditary Inclusion Body Myopathy (HIBM)

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:

Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive neuromuscular disorder 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/MNK) 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 HIBM muscle glycoproteins, resulting in muscle deterioration. To date, the amount of prospectively collected and published natural history data on HIBM 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
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Age 18-80 years, either gender, inclusive.
    2. Diagnosis of HIBM based upon a consistent clinical course and identification of GNE gene mutations. Molecular confirmation of the diagnosis will be obtained for all subjects in the study. Most subjects will be homozygous for the Iranian Jewish GNE mutation (p.M712T) in the kinase domain, but subjects with other mutations in the kinase (MNK) or the epimerase domain (GNE) as well as other ethnic backgrounds will also be eligible.
    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. An exception includes receiving a single dose of ManNac that may be given as part of the Phase 1 study of ManNAc for HIBM.

    4. Ability to travel to the NIH Clinical Center repeatedly for admissions.

EXCLUSION CRITERIA:

  1. Inability to stand and walk unassisted, with or without a gait aide for 2 minutes.
  2. Significant osteoarthritis affecting the ability to perform quantitative and functional studies of muscle strength.
  3. Psychiatric illness or neurological disease that would interfere with the subject s ability to comply with the requirements of this protocol. This includes uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, or panic disorder.
  4. 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.
  5. Presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic, or gastrointestinal disease not related to the primary disease process.
  6. Pregnancy or the possibility of pregnancy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01417533

Contacts
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
Investigators
Principal Investigator: Nuria Carrillo-Carrasco, M.D. National Human Genome Research Institute (NHGRI)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01417533     History of Changes
Other Study ID Numbers: 110218, 11-HG-0218
Study First Received: August 13, 2011
Last Updated: March 14, 2014
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
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on April 16, 2014