Gene Therapy for Gaucher's and Fabry Disease Using Viruses and Blood-Forming Cells
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|ClinicalTrials.gov Identifier: NCT00001234|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : March 4, 2008
|First Submitted Date ICMJE||November 3, 1999|
|First Posted Date ICMJE||November 4, 1999|
|Last Update Posted Date||March 4, 2008|
|Study Start Date ICMJE||January 1988|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Gene Therapy for Gaucher's and Fabry Disease Using Viruses and Blood-Forming Cells|
|Official Title ICMJE||Retroviral-Mediated Transfer and Expression of Glucocerebrosidase and Ceramidtrihexosidase (a-Galactosidase A) cDNA's in Human Hematopoietic Progenitor Cells|
Gaucher's disease is a lysosomal storage disease resulting from glycocerebroside GLUCOCEREBROSIDE (1) accumulation in macrophages due to a genetic deficiency of the enzyme glucocerebrosidase. It may occur in patients of all ages. The most severe form, Type 2 Gaucher's Disease occurs in infants who die in the first years of life (with rapidly progressive neurologic deterioration). The condition is passed from generation to generation through autosomal recessive inheritance.
Fabry's disease isa genetic disorder (X-linked recessive) due to the absence of the enzyme a-galactosidase A. The disease is characterized by abnormal collections of glycolipids in cells (histiocytes) within blood vessel walls, tumors on the thighs, buttocks, and genitalia(2) decreased sweating, tingling sensations in the extremities, and cataracts. Patients with Fabry's disease die from complications of the kidney, heart, or brain.
Both conditions are caused by the absence of specific enzymes (3). Patients with these conditions are missing (3) or have defective genes needed for the normal production of these enzymes. Studies on the blood-forming cells in bone marrow have lead to gene therapies using retroviruses as vehicles to carry and insert working genes into abnormal or diseased cells.
This study is designed to measure the safety and effectiveness of transferring working copies of genes responsible for making missing enzymes into the cells of patients with Gaucher's or Fabry disease.
|Detailed Description||This protocol was developed in order to obtain bone marrow stem cells for ex vivo transduction with retroviruses containing the human glucocerebrosidase gene. We continue to enter a small number of patients to this protocol each year. Studies with the bone marrow hematopoietic progenitor cells have enabled us to identify the most effective retroviral construct currently available in order to carry out gene therapy trials in patients with Gaucher's disease. The data revealed that a comparatively simple retroviral construct containing human glucocerebrosidase cDNA driven by the MoLV promoter is highly effective. We have obtained approval and initiated a Phase I safety and gene marking investigation in patients with Type I Gaucher's Disease.|
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Primary Purpose: Treatment|
|Condition ICMJE||Gaucher's Disease|
|Intervention ICMJE||Genetic: human glucocerebrosidase cDNA|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||April 2002|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Normal and patient volunteers.
Individuals with platelet counts less than 40,000/ul, PT greater than 15 seconds, or PTT greater than 40 seconds will not undergo bone marrow aspiration.
Individuals with hematologic disorders other than Gaucher Disease, Fabry Disease, or mild iron deficiency will not undergo bone marrow aspiration.
HIV positive individuals will be excluded from participating.
|Ages ICMJE||Child, Adult, Older Adult|
|Accepts Healthy Volunteers ICMJE||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00001234|
|Other Study ID Numbers ICMJE||880019
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||April 2002|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP