Bone Response to Enzyme Replacement in Gaucher's Disease
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: Gaucher's Disease
Intervention: CEREDASE™ (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Neurological Disorders and Stroke (NINDS)
Summary
The purpose of this study is to examine how the skeleton responds to repeated doses of enzyme
replacement therapy in patients with type I Gaucher's disease who have had their spleens
removed.
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.
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.
In this study patients will be divided into three groups. Each group will receive different
doses of enzyme replacement (Ceredase). In addition, two of the three groups will also
receive doses of a form of vitamin D (calcitriol). Researchers believe the groups receiving
vitamin D will have an improved response as compared to those patients only receiving enzyme
replacement.
Patients in each group who respond to enzyme replacement with increases in bone density will
be compared to the other treatment groups.
Clinical Details
Official title: Skeletal Responses to Macrophage-Targeted Glucocerebrosidase in Patients With Type 1 Gaucher's Disease
Study design: Treatment, Safety/Efficacy Study
Detailed description:
The purpose of this study is to examine the response of the skeleton to repeated infusions of
macrophage-targeted glucocerebrosidase (CEREDASE (Trademark) ) in splenectomized patients
with type I Gaucher's disease. The magnitude and rate of development of the skeletal
response will be monitored non-invasively. Theoretically, an enhanced response should occur
in patients supplemented with pharmacologic doses of 1, 25-dihydroxyvitamin D3 (calcitriol),
since calcium absorption and enzyme delivery to bone marrow macrophages should be increased
in this setting. These issues will be addressed in a clinical trial that uses a modified
factorial design. A total of 57 patients will be assigned to three treatment groups by block
randomization.
Group 1: CEREDASE (Trademark) (60 IU/kg q2wks; 0-6 months)
CEREDASE (Trademark) (30 IU/kg q2wks; 7-24 months)
Group 2: Calcitriol (0. 25-3. 0 micrograms/day; 0-24 months)
CEREDASE (Trademark) (60 IU/kg q2wks; 7-12 months)
CEREDASE (Trademark) (30 IU/kg q2wks; 13-24 months)
Group 3: Calcitriol (0. 25-3. 0 micrograms/day; 0-24 months)
CEREDASE (Trademark) (60 IU/kg q2wks; 0-6 months)
CEREDASE (Trademark) (30 IU/kg q2wks; 7-24 months)
The number of patients responding to enzyme replacement with a significant decrease in
hepatic volume and a significant increase in trabecular bone density of the lumbar spine will
be compared between the treatment groups.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Splenectomized Gaucher patients.
Aged 18-45 who have not received enzyme therapy for at least 1 year.
No patients with other illnesses (pulmonary, liver, kidney, bone, hematologic).
Locations and Contacts
National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Rosenthal DI, Barton NW, McKusick KA, Rosen BR, Hill SC, Castronovo FP, Brady RO, Doppelt SH, Mankin HJ. Quantitative imaging of Gaucher disease. Radiology. 1992 Dec;185(3):841-5. 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.
Starting date: December 1993
Ending date: November 2000
Last updated: March 3, 2008
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