High-Dose Intravenous Immunoglobulin to Treat Cerebellar Degeneration
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Spinocerebellar Degenerations
Intervention: high-dose intravenous immunoglobulin (IVIG) (Drug)
Phase: Phase 2
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)
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.
Official title: The Efficacy of High-Dose Intravenous Immunoglobulin Therapy In Patients With Cerebellar Degeneration: A Double Blind, Placebo Controlled Trial
Study design: Treatment, Safety/Efficacy Study
There is increasing evidence that there is an antibody mediated, autoimmune component in
hereditary and sporadic cerebellar degeneration. The objective of this study is to show
clinical improvement or stabilization in ataxia using treatment with intravenous
immunoglobulin (IVIG) treatment. This study is a clinical, randomized, placebo-controlled
trial of IVIG in adult patients with cerebellar ataxia. Patients will be selected from the
motor control clinic based on a diagnosis of sporadic or hereditary cerebellar degeneration.
Study drug (placebo versus active) will be given in an intravenous infusion over a 2-day
period while the patient is hospitalized. This will be repeated monthly for 2 months.
Efficacy measurement will include clinical ataxia rating scales, motor speed testing and
clinical gait evaluation. These will be performed at baseline, during each hospitalization,
and 1 month following final IVIG infusion. Main outcome measure will be difference from
baseline in score on the NINDS ataxia rating scale 1 month following 2 treatments of 2 mg/kg
IVIG (total 4 mg/kg).
Minimum age: N/A.
Maximum age: N/A.
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
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,
Locations and Contacts
National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland 20892, United States
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.
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.
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. Review.
Starting date: April 2002
Ending date: February 2004
Last updated: March 3, 2008