Type 2 Gaucher Disease Clinical Trial
Official title:
Direct Convection-Enhanced Delivery of Glucocerebrosidase for the Treatment of Type 2 (Acute Neuronopathic) Gaucher Disease
| Verified date | November 3, 2006 |
| Source | National Institutes of Health Clinical Center (CC) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
This study will use an experimental method of delivering the enzyme glucocerebrosidase
directly into the brain of a patient with Gaucher disease to treat disease symptoms. Patients
with Gaucher disease have insufficient levels of glucocerebrosidase. As a result, substances
normally broken down by this enzyme accumulate in the body, causing damage to the brain and
other organs. Symptoms of Gaucher disease outside the brain can be treated by infusing the
missing enzyme intravenously (IV, through a vein). However, IV infusions do not help the
neurologic symptoms of the disease, because the enzyme cannot get into the brain. This study
will use a new technique called convection-enhanced delivery to try to introduce
glucocerebrosidase directly into the brain.
This single-patient study includes an 8-month-old male with Type 2 Gaucher disease with
progressive neurological decline.
In preparation for the enzyme infusion, the patient will have a complete physical
examination, including a detailed neurological examination, and blood and urine tests. On the
day of surgery, the child will be placed under general anesthesia for magnetic resonance
imaging (MRI) of the brain. MRI uses a magnetic field and radio waves to produce images of
body tissues and organs. For this procedure, the child lies on a table that is moved into the
scanner (a narrow cylinder), wearing earplugs to protect his hearing from the loud knocking
and thumping sounds that occur during the scanning process. He will then be brought to the
operating room for the infusion procedure, as follows:
An incision will be made in the scalp and a small hole drilled through the skull. Then, a
small tube (cannula) will be positioned through the hole into the target area in the brain.
Once the tip of the cannula is in place, it will be connected with tubing to a syringe filled
with glucocerebrosidase in saline (salt water). The child will then have a second MRI scan to
make sure the cannula is placed correctly and to monitor delivery of the glucocerebrosidase
to the brain. The child will be monitored closely with MRI scans every 30 to 60 minutes
during the infusion to look for fluid in the brain and determine the extent of the enzyme
perfusion. The infusion will last no longer than 6 hours and will be stopped when the full
dose of enzyme has been delivered. The cannula will be removed and the scalp incision closed.
The child will stay in the hospital for observation from 4 to 10 days, with at least 24 hours
in the intensive care unit and 3 to 7 days in the pediatric unit.
The child will be seen in the clinic two weeks after discharge and then once a month for 3
months to evaluate any possible effects of the surgery. These follow-up visits include a
repeat MRI scan and neurological examination. After the first 3 months, visits may be less
frequent.
If the child continues to have symptoms during the course of follow-up or his neurologic
status worsens, additional enzyme infusions will be offered, possibly including treatment of
the brainstem. If the child gains no benefit after three infusions have been performed, no
additional infusions will be offered. If there appears to be any neurological benefit,
additional infusions may be offered.
| Status | Completed |
| Enrollment | 1 |
| Est. completion date | November 3, 2006 |
| Est. primary completion date | |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | N/A to 5 Years |
| Eligibility |
- INCLUSION CRITERIA The patient is eligible because he has Type 2 Gaucher disease. EXCLUSION CRITERIA The patient may not be eligible to receive CED of glucocerebrosidase if he: 1. Is not healthy enough to undergo surgery or general anesthesia. 2. Has an uncorrectable bleeding disorder. 3. Is not able to undergo magnetic resonance (MR)-imaging. |
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institute of Neurological Disorders and Stroke (NINDS) | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) |
United States,
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. — View Citation