Intravenous Immune Globulin to Treat Hereditary Inclusion Body Myopathy

NCT00195637 | Completed Phase 1

• 2 other identifiers: 05023605-HG-0236
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate patients with Hereditary Inclusion Body Myopathy (HIBM) and examine the effects of immune globulin (IG) treatment on muscle and muscle function. HIBM is a progressive neuromuscular disease that begins in early adulthood, primarily affecting limb muscles. It results from mutations of the gene that is responsible for producing sialic acid, a sugar normally found on the surface of certain proteins, including alpha-dystroglycan, which is involved in muscle function. Some patients with HIBM have decreased sialic acid on the alpha-dystroglycan protein, which may be the cause of their muscle weakness. IG is a protein in the blood that carries a large amount of sialic acid. This study will administer IG to patients with HIBM and determine if the sialic acid in IG is taken up by muscle cells in these patients and if it can restore some of their muscle function. Four patients with HIBM will be admitted to this study at the NIH Clinical Center for evaluation and IG treatment. The evaluation lasts about 1 month. After completing baseline studies (see below), patients receive two intravenous doses of immune globulin (on days 6 and 7), followed by measurement of muscle strength 2 days later (day 9). They receive additional IG infusions on days 13, 20, and 27. A final set of tests is performed on day 29. Patients may leave the hospital on pass when no studies are being done. A patient's initial evaluation includes:

• History and physical examination, neurological examination, eye examination
• 24-hour urine collection
• Blood tests on two separate days
• Photographs showing the extent of muscle affected
• Chest x-ray, electrocardiogram (EKG), and echocardiogram
• Two muscle biopsies, one before and one after the IG treatments. For this procedure, a small sample of muscle tissue is surgically removed for examination under the microscope.
• Muscle strength and endurance testing, including the following: The patient uses pulleys attached to machines that measure the strength of 24 different muscle groups The patient walks for 6 minutes and performs exercises To evaluate swallowing, the patient swallows a thick substance called barium The patient's tongue strength is measured using a specialized instrument.
• Magnetic resonance imaging (MRI) of the muscles of the thigh or calf: MRI uses a magnetic field and radio waves to produce detailed pictures of organs and tissues. During the scan, the subject lies on a table in a narrow cylinder containing a magnetic field, wearing ear plugs to muffle loud noises that occur with electrical switching of the magnetic fields. He or she can speak with a staff member via an intercom system at all times during the procedure. The neurological and muscle strength and endurance evaluations are repeated on study days 9 and 29.

Conditions

Hereditary Inclusion Body Myopathy

Keywords

GNE Gene; Alpha-Dystroglycan; Sialic Acid; Glycosylation; Dystroglycanopathy; Hereditary Inclusion Body Myopathy; Immune Globulin; HIBM

Interventions

Immune Globulin DRUG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70 years, either gender
• Diagnosis of HIBM based upon a consistent clinical course plus either convincing muscle histology or identification of GNE gene mutations
• Ability to travel to the NIH Clinical Research Center for admissions

You may not qualify if:

• Age less than18 or greater than 70, pregnancy
• Previous adverse reaction to IvIg that did not resolve with acetaminophen or benadryl treatment
• History of myocardial infarction, stroke, or kidney disease
• Psychiatric illness or neurological disease that interferes with compliance or communication with health care personnel
• Current malignancy
• Uncontrolled hypertension (blood pressure greater than180 systolic or greater than 95 diastolic)
• Electrocardiogram changes indicative of myocardial infarction, arrhythmia, tachycardia, bradycardia, left bundle branch block
• Chest radiographic abnormalities, including an infiltrate, mass, congestive heart failure, embolism, atelectasis
• Serum potassium less than 3.0 mEq/L
• Serum creatinine greater than 2.0 mg/dL
• SGPT or SGOT greater than 70 U/L
• Hemoglobin less than 10.0 g/dL
• Platelets less than100 k/mm(3)
• WBC less than 3.0 k/microliters
• ESR greater than100 mm/h

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR, Rowland LP. Inclusion body myositis and myopathies. Ann Neurol. 1995 Nov;38(5):705-13. doi: 10.1002/ana.410380504. No abstract available.

  PMID: 7486861 BACKGROUND

• Sadeh M, Gadoth N, Hadar H, Ben-David E. Vacuolar myopathy sparing the quadriceps. Brain. 1993 Feb;116 ( Pt 1):217-32. doi: 10.1093/brain/116.1.217.

  PMID: 8453459 BACKGROUND

• Sivakumar K, Dalakas MC. The spectrum of familial inclusion body myopathies in 13 families and a description of a quadriceps-sparing phenotype in non-Iranian Jews. Neurology. 1996 Oct;47(4):977-84. doi: 10.1212/wnl.47.4.977.

  PMID: 8857730 BACKGROUND

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Interventions

Immunoglobulins

Intervention Hierarchy (Ancestors)

Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• William A Gahl, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2005
• First Posted: September 19, 2005
• Study Start: September 16, 2005
• Primary Completion: July 3, 2006
• Study Completion: July 3, 2006
• Last Updated: December 4, 2019

Record last verified: 2018-05-22

Locations

US (1)