Effects of Enzyme Replacement in Gaucher's Disease

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001289
First received: November 3, 1999
Last updated: April 21, 2010
Last verified: March 2008
  Purpose

Gaucher disease is a lysosomal storage disease resulting from glycocerebroside accumulation in macrophages due to a genetic deficiency of the enzyme glucocerebrosidase. It may occur in adults but occurs most severely in infants, in whom cerebroside also accumulates in neurons. Patients with Gaucher's disease experience enlargement of the liver and spleen and bone destruction. The condition is passed from generation to generation through autosomal recessive inheritance. There are actually three types of Gaucher's disease.

Type I is the most common form. It is a chronic non-neuronopathic form, meaning the disease does not affect nerve cells. The symptoms of type I can appear at any age.

Type II appears in infancy and usually results in death for the patient. Type II is an acute neuronopathic form and can affect the brain stem. It is the most severe form of the disease.

Type III is also neuronopathic, however it is subacute in nature. This means the course of the illness lies somewhere between long-term (chronic) and short-term (acute).

The purpose of this study is to examine the effects of enzyme replacement therapy on patients with Gaucher's disease, specifically those types directly affecting the nervous system (neuronopathic).

Patients with Gaucher's disease types II and III will be selected to participate in the study and receive enzyme replacement therapy. Patients participating will undergo a variety of tests to measure levels of hemoglobin concentration, liver volume, and spleen volume. Improvements in these measures will be compared other laboratory tests measuring the involvement of the nervous system.


Condition
Gaucher's Disease

Study Type: Observational
Official Title: Clinical and Biochemical Effects of Macrophage-Targeted Glucocerebrosidase on Neurological Involvement in Neuronopathic Gaucher's Disease

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 70
Study Start Date: September 1991
Estimated Study Completion Date: March 2008
Detailed Description:

The purpose of this study is to examine the effects of enzyme replacement therapy in patients with neuronopathic Gaucher's disease and to investigate the pathogenesis of their neurological signs and symptoms. Macrophage-targeted glucocerebrosidase will be administered by intravenous infusion under the supervision of the patient's private physician at an initial dosage of 60 to 120 IU per kg of body weight weekly or every other week. Patients will be categorized as treatment responders if they display a clinically significant increase in hemoglobin concentration and a reduction in hepatic or splenic volume. Improvement in these parameters over time will be correlated with measurements for metabolic encephalopathy and radiologic, electrophysiologic and psychometric measurements of neurological involvement.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. All patients with neuropathic Gaucher's disease who have a partial or complete horizontal supranuclear gaze palsy or a genotype associated with neurological involvement.
    2. All candidates must be serologically nonreactive for hepatitis B and human immunodeficiency (AIDS) virus. HIV positive patients will be excluded because of the effects of the latter illness on cognitive performance.
    3. Individuals with neoplastic disease will be excluded.
    4. The general health and well being of each candidate must be sufficient to allow for a modest amount of blood drawing, collection of appropriate urine and spinal fluid specimens and performance of necessary roentgenographic and magnetic resonance (MR) imaging studies. In addition, each candidate must be able to return to the National Institutes of Health (NIH) on a regular basis dictated by disease severity for monitoring of laboratory parameters.

EXCLUSION CRITERIA:

  1. Patient who participates in a clinical study of an investigational therapeutic agent for Gaucher Disease.
  2. Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
  3. Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001289

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00001289     History of Changes
Other Study ID Numbers: 910225, 91-N-0225
Study First Received: November 3, 1999
Last Updated: April 21, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Enzyme Replacement
Type 3 Gaucher's Disease
Lysosomal Storage
Supranuclear Gaze Palsy
Seizures
Mental Retardation
Gaucher Disease

Additional relevant MeSH terms:
Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Sphingolipidoses
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on August 25, 2014