Phase I Study in the Safety and Efficacy of Transduced Keratinocytes for Possible Treatment of Gyrate Atrophy
Gene therapy
Eye Diseases+4
+ Congenital, Hereditary, and Neonatal Diseases and Abnormalities
+ Uveal Diseases
Treatment Study
Summary
Study start date: April 1, 1998
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.5 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Elevated serum ornithine level greater than or equal to 200 micro M, as measured by the median of three values obtained monthly for two months prior to the screening visit and at the screening visit. Absence of OAT activity measured by western blot analysis and isolated enzyme activity in skin biopsy samples. Fundus findings indicative of gyrate atrophy as characterized by sharply demarcated circular patches of chorioretinal atrophy. Must be at least 18 years of age. Female patients of child bearing potential must have a pregnancy test done, which demonstrates a negative result and must agree to practice effective birth control for 12 months following study initiation, or until patch removal, whichever comes first. Must sign and date the informed consent and is willing and able to follow study procedures. Patients demonstrates progression of ocular disease due to grate atrophy evidenced by reduction in electrophysiologic testing, visual field testing or progression of retinal findings. Patient has been offered an arginine-restricted diet and is unable to attain ornithine levels less than 200 micro M prior to patch placement. Patient has previously undergone a skin biopsy. Not currently participating in other experimental protocols or therapeutic trials. Does not have a known malignancy or chronic infection yielding immunoincompetence. Patient must be able to maintain follow-up and follow details of the protocol.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location