Bone Response to Enzyme Replacement in Gaucher's Disease

Status Completed

Clinical Trial 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 Trial 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. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT00001416
Study type	Interventional
Source	National Institutes of Health Clinical Center (CC)
Contact
Status	Completed
Phase	Phase 2
Start date	December 1993
Completion date	November 2000

View Details

See also
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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.