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Effects of Enzyme Replacement in Gaucher's Disease

Primary Purpose

Gaucher's Disease

Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
Sponsored by
National Institute of Neurological Disorders and Stroke (NINDS)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Gaucher's Disease focused on measuring Enzyme Replacement, Type 3 Gaucher's Disease, Lysosomal Storage, Supranuclear Gaze Palsy, Seizures, Mental Retardation, Gaucher Disease

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: All patients with neuropathic Gaucher's disease who have a partial or complete horizontal supranuclear gaze palsy or a genotype associated with neurological involvement. 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. Individuals with neoplastic disease will be excluded. 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: Patient who participates in a clinical study of an investigational therapeutic agent for Gaucher Disease. 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. Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
June 30, 2017
Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
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1. Study Identification

Unique Protocol Identification Number
NCT00001289
Brief Title
Effects of Enzyme Replacement in Gaucher's Disease
Official Title
Clinical and Biochemical Effects of Macrophage-Targeted Glucocerebrosidase on Neurological Involvement in Neuronopathic Gaucher's Disease
Study Type
Observational

2. Study Status

Record Verification Date
March 3, 2008
Overall Recruitment Status
Completed
Study Start Date
September 23, 1991 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 3, 2008 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gaucher's Disease
Keywords
Enzyme Replacement, Type 3 Gaucher's Disease, Lysosomal Storage, Supranuclear Gaze Palsy, Seizures, Mental Retardation, Gaucher Disease

7. Study Design

Enrollment
70 (false)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: All patients with neuropathic Gaucher's disease who have a partial or complete horizontal supranuclear gaze palsy or a genotype associated with neurological involvement. 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. Individuals with neoplastic disease will be excluded. 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: Patient who participates in a clinical study of an investigational therapeutic agent for Gaucher Disease. 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. Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures.
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
2023606
Citation
Barton NW, Brady RO, Dambrosia JM, Di Bisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991 May 23;324(21):1464-70. doi: 10.1056/NEJM199105233242104.
Results Reference
background
PubMed Identifier
21799847
Citation
Benko W, Ries M, Wiggs EA, Brady RO, Schiffmann R, Fitzgibbon EJ. The saccadic and neurological deficits in type 3 Gaucher disease. PLoS One. 2011;6(7):e22410. doi: 10.1371/journal.pone.0022410. Epub 2011 Jul 20.
Results Reference
derived

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Effects of Enzyme Replacement in Gaucher's Disease

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