NCT00195637

Intravenous Immune Globulin to Treat Hereditary Inclusion Body Myopathy

Completed Phase 1 Last updated 4 December 2019

What this trial tests

Phase 1 trial testing Immune Globulin in Hereditary Inclusion Body Myopathy in 4 participants. Completed in 3 July 2006.

Timeline

16 September 2005

Primary endpoint
3 July 2006

3 July 2006

Quick facts

Lead sponsor	National Human Genome Research Institute (NHGRI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	4
Start date	16 September 2005
Primary completion	3 July 2006
Estimated completion	3 July 2006
Sites	1 location across United States

Drugs / interventions tested

• Immune Globulin — full drug profile →

Conditions studied

• Hereditary Inclusion Body Myopathy — all drugs for Hereditary Inclusion Body Myopathy →

Sponsor

National Human Genome Research Institute (NHGRI)

Who can join

Adults 18 to 70, any sex, with Hereditary Inclusion Body Myopathy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. GNE myopathy: current update and future therapy.
   Nishino I, Carrillo-Carrasco N, Argov Z. · · 2015 · cited 121× · PMID 25002140 · DOI 10.1136/jnnp-2013-307051
2. Mutation update for GNE gene variants associated with GNE myopathy.
   Celeste FV, Vilboux T, Ciccone C, de Dios JK, et al · · 2014 · cited 95× · PMID 24796702 · DOI 10.1002/humu.22583
3. UDP-GlcNAc 2-Epimerase/ManNAc Kinase (GNE): A Master Regulator of Sialic Acid Synthesis.
   Hinderlich S, Weidemann W, Yardeni T, Horstkorte R, et al · · 2015 · cited 86× · PMID 23842869 · DOI 10.1007/128_2013_464
4. Hereditary inclusion body myopathy: a decade of progress.
   Huizing M, Krasnewich DM. · · 2009 · cited 71× · PMID 19596068 · DOI 10.1016/j.bbadis.2009.07.001
5. GNE Myopathy: Etiology, Diagnosis, and Therapeutic Challenges.
   Carrillo N, Malicdan MC, Huizing M. · · 2018 · cited 69× · PMID 30338442 · DOI 10.1007/s13311-018-0671-y
6. CDG Therapies: From Bench to Bedside.
   Brasil S, Pascoal C, Francisco R, Marques-da-Silva D, et al · · 2018 · cited 66× · PMID 29702557 · DOI 10.3390/ijms19051304
7. Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy.
   Leoyklang P, Malicdan MC, Yardeni T, Celeste F, et al · · 2014 · cited 21× · PMID 25123033 · DOI 10.2217/bmm.14.2
8. Biosynthetic and genetic pathways related to sialic acid metabolism.
   Huang S, van de Ven EGP, Tee T, Lefeber DJ. · · 2026 · PMID 41655697 · DOI 10.1016/j.jbc.2026.111262