Clinical Trial: Bone Response to Enzyme Replacement in Gaucher's Disease
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Skeletal Responses to Macrophage-Targeted Glucocerebrosidase in Patients With Type 1 Gaucher's Disease
Brief 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.
Detailed Summary:
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.
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: November 3, 1999
Date Started: December 1993
Date Completion: November 2000
Last Updated: September 21, 2016
Last Verified: September 2016
