Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001735
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Gene Therapy for Gyrate Atrophy
Sponsor:
National Eye Institute NEI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase I Study in the Safety and Efficacy of Transduced Keratinocytes for Possible Treatment of Gyrate Atrophy
Status:
COMPLETED
Status Verified Date:
2000-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the safety and effectiveness of gene therapy for patients with gyrate atrophy an inherited condition in which areas of the retina-the inner lining of the wall of the eye-become thin Over several decades this degeneration of the retina causes tunnel vision night blindness and other vision problems
Gyrate atrophy is caused by a defect in the gene responsible for producing an enzyme ornithine aminotransferase OAT that breaks down an amino acid called ornithine As a result excessive ornithine buildup causes the retinal thinning Currently this condition can only be treated with amino acid tablets and a very low-protein diet with limited fruits and vegetables and more than 2000 calories a day from carbohydrates and fats Some patients cannot maintain this diet and they need another treatment One possible alternative is to replace the defective gene with one that functions normally
Patients who have been followed in NEIs Ocular Genetics service may be eligible to participate in this study Study patients will undergo the following gene therapy procedure
1 Skin biopsy-A small piece of skin is surgically removed from the patients thigh
2 Gene transfer-Skin cells called keratinocytes are taken from the biopsied tissue and grown in the laboratory The normal gene that produces OAT is inserted into the cells causing them to produce more of the enzyme
3 Skin graft-Under local anesthesia a patch of skin about 2 14 inches x 2 14 inches is surgically removed from the upper thigh and some of the cells with increased OAT are grafted back onto this area
Patients will be followed at 1 week and 2 weeks after the procedure then monthly for 6 months again at 9 months and 1 year Follow-up will continue at 1-year intervals in patients in whom the treatment is successful During each follow-up visit patients will have 2 to 3 tablespoons of blood drawn for tests A small biopsy about 14 inch of transplanted cells will also be done at 1 week 1 month 3 months 6 months 1 year and each year or so thereafter These tests will evaluate whether the treated skin cells are producing the deficient OAT enzyme and if so how much and for how long They will also indicate whether the enzyme produced is sufficient to lower ornithine blood levels Patients will also undergo various eye examinations before grafting and at scheduled follow-up visits These tests may include electrophysiologic ERG testing fundus photographs scanning laser ophthalmoscope visual field test fluorescein angiogram visual acuity and manifest reaction
Gyrate atrophy is caused by a defect in the gene responsible for producing an enzyme ornithine aminotransferase OAT that breaks down an amino acid called ornithine As a result excessive ornithine buildup causes the retinal thinning Currently this condition can only be treated with amino acid tablets and a very low-protein diet with limited fruits and vegetables and more than 2000 calories a day from carbohydrates and fats Some patients cannot maintain this diet and they need another treatment One possible alternative is to replace the defective gene with one that functions normally
Patients who have been followed in NEIs Ocular Genetics service may be eligible to participate in this study Study patients will undergo the following gene therapy procedure
1 Skin biopsy-A small piece of skin is surgically removed from the patients thigh
2 Gene transfer-Skin cells called keratinocytes are taken from the biopsied tissue and grown in the laboratory The normal gene that produces OAT is inserted into the cells causing them to produce more of the enzyme
3 Skin graft-Under local anesthesia a patch of skin about 2 14 inches x 2 14 inches is surgically removed from the upper thigh and some of the cells with increased OAT are grafted back onto this area
Patients will be followed at 1 week and 2 weeks after the procedure then monthly for 6 months again at 9 months and 1 year Follow-up will continue at 1-year intervals in patients in whom the treatment is successful During each follow-up visit patients will have 2 to 3 tablespoons of blood drawn for tests A small biopsy about 14 inch of transplanted cells will also be done at 1 week 1 month 3 months 6 months 1 year and each year or so thereafter These tests will evaluate whether the treated skin cells are producing the deficient OAT enzyme and if so how much and for how long They will also indicate whether the enzyme produced is sufficient to lower ornithine blood levels Patients will also undergo various eye examinations before grafting and at scheduled follow-up visits These tests may include electrophysiologic ERG testing fundus photographs scanning laser ophthalmoscope visual field test fluorescein angiogram visual acuity and manifest reaction
Detailed Description:
The primary purpose of this phase I study is to evaluate the safety of a skin engraftment procedure for transplanting ex-vivo transduced keratinocytes in patients with a deficiency of the ornithine transferase gene OAT The safety of this procedure will be evaluated in terms of technical complications and the immune response of the patient to the presence of the transduced keratinocytes Adult patients with gyrate atrophy a disease defined by a deficiency of OAT who have been followed for an extended period of time at the National Eye Institute and whose natural history is known to the investigators will be evaluated for study enrollment Keratinocytes previously obtained and grown in culture from these patients will be transduced with a retrovirus manufactured under GMP conditions to express the OAT gene The autologous transduced keratinocytes will be returned to the patient on the upper thigh in a small patch prepared to receive graft At study defined visits the site integrity will be monitored and biopsies of the grafted areas will be performed The biopsies will provide information to evaluate the following three secondary study objectives 1 the ability of keratinocytes to express the OAT gene 2 the extent and duration of such expression and 3 the extent to which the activity present in the keratinocytes is sufficient to lower serum levels of ornithine
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 98-EI-0088 | None | None | None |