High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration

NCT00034242 | Completed Phase 2

• 2 other identifiers: 02018502-N-0185
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine whether high-dose intravenous immunoglobulin (IVIG) is safe and effective for treating cerebellar ataxia-degeneration of the cerebellum, the part of the brain responsible for coordinating muscle movements and balance. The disease causes a slowly progressive impairment of speech and balance, with patients often developing slurred speech, tremor, clumsiness of the hands, and walking difficulties (ataxia). IVIG is derived from donated blood that has been purified, cleaned and processed into a form that can be infused. IVIG is an immune suppressant that is routinely used to treat other neurological conditions. Patients 18 years of age and older with hereditary (genetic) or sporadic (unknown cause) cerebellar degeneration may be eligible for this 5-month study. They must have evidence of an immune component to their condition, such as gluten sensitivity or antiganglioside antibodies. Candidates will be screened with a neurological examination, a review of medical records and possibly blood tests. Participants will be randomly assigned to receive infusions of either IVIG or placebo (an inactive substance) through an arm vein once a month for two months. The infusions will be given in the hospital in doses divided over 2 days, each lasting 6 to 10 hours. Before the infusions, patients will undergo ataxia assessments through tests of coordination and balance that may involve finger tapping, walking in a straight line, talking, and eye movements. When the treatment is finished, patients will be followed in the clinic once a month for 3 months for blood tests repeat ataxia assessments to evaluate the effects of treatment.

Conditions

Spinocerebellar Degenerations

Keywords

Ataxia; Treatment; IVIG; SCA; Cerebellar Degeneration; Cerebellar Ataxia; Cerebellum

Interventions

high-dose intravenous immunoglobulin (IVIG) DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults over 18 with hereditary or sporadic cerebellar degeneration. Sporadic cerebellar degeneration may include the cerebellar predominant variant of Multiple System Atrophy (MSA-C). Hereditary ataxia is limited to the SCAs (spinocerebellar ataxias) or those patients with clear autosomal dominant ataxia. Patients must also have evidence for an immune component to their condition such as gluten-sensitivity or antiganglioside antibodies.

You may not qualify if:

• Patients on the gluten-free diet. Those who wish to participate in this trial must be off the diet for a period of 3 months prior to the start of the study.
• Patients with Friedreich's ataxia. To date, this has not been associated with autoimmune phenomena. We would not expect this population to respond.
• Patients with other autosomal recessive and mitochondrial forms of ataxia, since autoimmunity has not been studied in this population.
• Patients with hypercoaguable disorders. This includes conditions like Protein C or S deficiency, underlying malignancy and/or paraproteinemia.
• Patient with acute renal insufficiency or patients on known nephrotoxic drugs.
• Patients with selective IgA deficiency
• Known paraneoplastic cerebellar degeneration.
• Cerebellar ataxia that is congenital, static and/or symptomatic (due to stroke, tumor, demyelinating or infectious).
• Women who are pregnant or lactating. Those of child-bearing age will be asked to use effective contraception for the duration of the study.
• Those patients who do not wish to use a product derived from human serum (for example, Jehovah's Witness).

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institute of Neurological Disorders and Stroke (NINDS)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Arakawa Y, Yoshimura M, Kobayashi S, Ichihashi K, Miyao M, Momoi MY, Yanagisawa M. The use of intravenous immunoglobulin in Miller Fisher syndrome. Brain Dev. 1993 May-Jun;15(3):231-3. doi: 10.1016/0387-7604(93)90071-f.

  PMID: 8214351 BACKGROUND

• Bech E, Orntoft TF, Andersen LP, Skinhoj P, Jakobsen J. IgM anti-GM1 antibodies in the Guillain-Barre syndrome: a serological predictor of the clinical course. J Neuroimmunol. 1997 Jan;72(1):59-66. doi: 10.1016/s0165-5728(96)00145-2.

  PMID: 9003245 BACKGROUND

• Burk K, Bosch S, Muller CA, Melms A, Zuhlke C, Stern M, Besenthal I, Skalej M, Ruck P, Ferber S, Klockgether T, Dichgans J. Sporadic cerebellar ataxia associated with gluten sensitivity. Brain. 2001 May;124(Pt 5):1013-9. doi: 10.1093/brain/124.5.1013.

  PMID: 11335703 BACKGROUND

MeSH Terms

Conditions

Spinocerebellar Degenerations; Ataxia; Cerebellar Ataxia

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 24, 2002
• First Posted: April 24, 2002
• Study Start: April 1, 2002
• Study Completion: February 1, 2004
• Last Updated: March 4, 2008

Record last verified: 2004-02

Locations

US (1)