Ignite Creation Date:
2024-05-05 @ 9:57 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001535
Status:
COMPLETED
Last Update Posted:
2008-02-08
First Post:
1999-11-03
Brief Title:
Twins Study of Gene Therapy for HIV Infection
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Gene Therapy for AIDS Using Retroviral Mediated Gene Transfer to Deliver HIV-1 Anti-Sense TAR and Transdominant Rev Protein Genes to Syngeneic Lymphocytes in HIV-1 Infected Identical Twins
Status:
COMPLETED
Status Verified Date:
2002-03
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 test the safety and effectiveness of genetically altered T lymphocytes white blood cells of the immune system in reducing viral load in patients infected with the human immunodeficiency virus HIV The lymphocytes will have two genes inserted into them a laboratory-manufactured anti-HIV gene designed to inhibit HIV reproduction either the RevTD or Rev-TD-antiTAR gene and a marker gene that will show whether or not the inserted genes have gotten into the cells
Identical twin pairs 18 years of age and older- one of whom is HIV-positive infected with the human immunodeficiency virus and the other HIV-negative not infected may be eligible for this study
All participants will have a complete medical history and physical examination blood tests and a tetanus booster shot if indicated The non HIV-infected twin will then undergo lymphapheresis to collect lymphocytes In this procedure whole blood is collected through a needle placed in an arm vein The blood circulates through a machine that separates it into its components The lymphocytes are then removed and the red cells and plasma are returned to the donor either through the same needle or through a second needle placed in the other arm
The donor cells are grown in the laboratory for a few days and then the new genes are inserted into them The genetically altered cells are grown in the laboratory for several days until their numbers increase approximately a thousand-fold They are then infused intravenously through a vein into the infected twin These procedures-lymphapheresis gene modification and infusion-will be repeated at approximately 2-month intervals up to four times
Each lymphocyte infusion takes about 60 minutes The patients vital signs temperature pulse blood pressure and breathing are monitored frequently during the infusion and hourly for 4 hours after the infusion Blood samples are taken the day of the infusion 3 days later and then weekly to monitor the gene-modified cells immune status viral activity and other factors These tests may be done less often as the study progresses and more is learned about the safety of the infusions The infusions are done on an outpatient basis unless side effects require that they be done in the hospital with post-infusion monitoring for at least 24 hours
Patients will be followed for long-term effects of treatment monthly for the first 3 months once a month for the next 9 months and yearly from then on
This study will contribute information about the use and side effects of gene therapy in HIV infection that may lead to new treatment strategies A potential direct benefit to HIV-infected individuals participating in this study is reduced viral load in laboratory studies the RevTD and Rev-TD-antiTAR genes have inhibited HIV spread in the test tube However this is an early phase of study and the likelihood of receiving this benefit is unknown
Identical twin pairs 18 years of age and older- one of whom is HIV-positive infected with the human immunodeficiency virus and the other HIV-negative not infected may be eligible for this study
All participants will have a complete medical history and physical examination blood tests and a tetanus booster shot if indicated The non HIV-infected twin will then undergo lymphapheresis to collect lymphocytes In this procedure whole blood is collected through a needle placed in an arm vein The blood circulates through a machine that separates it into its components The lymphocytes are then removed and the red cells and plasma are returned to the donor either through the same needle or through a second needle placed in the other arm
The donor cells are grown in the laboratory for a few days and then the new genes are inserted into them The genetically altered cells are grown in the laboratory for several days until their numbers increase approximately a thousand-fold They are then infused intravenously through a vein into the infected twin These procedures-lymphapheresis gene modification and infusion-will be repeated at approximately 2-month intervals up to four times
Each lymphocyte infusion takes about 60 minutes The patients vital signs temperature pulse blood pressure and breathing are monitored frequently during the infusion and hourly for 4 hours after the infusion Blood samples are taken the day of the infusion 3 days later and then weekly to monitor the gene-modified cells immune status viral activity and other factors These tests may be done less often as the study progresses and more is learned about the safety of the infusions The infusions are done on an outpatient basis unless side effects require that they be done in the hospital with post-infusion monitoring for at least 24 hours
Patients will be followed for long-term effects of treatment monthly for the first 3 months once a month for the next 9 months and yearly from then on
This study will contribute information about the use and side effects of gene therapy in HIV infection that may lead to new treatment strategies A potential direct benefit to HIV-infected individuals participating in this study is reduced viral load in laboratory studies the RevTD and Rev-TD-antiTAR genes have inhibited HIV spread in the test tube However this is an early phase of study and the likelihood of receiving this benefit is unknown
Detailed Description:
This phase III pilot study will evaluate the safety relative survival and potential efficacy of infusions of activated genetically engineered syngeneic CD4 T lymphocytes obtained from HIV-1 seronegative identical twins T cells from each seronegative twin will be obtained by apheresis enriched for CD4 cells induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation divided into aliquots which will then be individually transduced with a control retroviral vector and up to two additional retroviral vectors containing potentially therapeutic genes antisense TAR andor transdominant Rev These engineered T cell populations will be expanded 10-1000 fold in numbers during 1-2 weeks of culture and then will be infused into the seropositive twins The relative survival of the uniquely engineered T cell populations will be monitored by vector-specific PCR while the recipients functional immune status is monitored by standard in vitro and in vivo testing protocols A total of up to 4 cycles of treatment may be given using identical or different combinations of control and anti-HIV-1 retroviral vectors
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 |
|---|---|---|---|
| 96-HG-0051 | None | None | None |