Efficacy Study of T Cell Vaccination in HIV Infection
1. december 2009 opdateret af: Soroka University Medical Center
Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection
The hallmark of HIV infection and AIDS is the continuous attrition of CD4 T cells.
One of the mechanisms that may account for the CD4 attrition , is autoimmunity against the CD4 T cells, caused by autologous immune cells.
Vaccination against autoimmune reactive T cells has been successfully tried in animal models of autoimmune diseases and is now being tried in patients with Multiple Sclerosis.
The purpose of the present study is to test this hypothesis in HIV infection.
We will vaccinate HIV infected patients in whom specific autoimmune reactivity against CD4 is present , with their own CD4 reactive T cells.
Following that, we shall study the patients and find out if the T cell vaccination caused a rise in CD4 T cell levels, and whether it influenced HIV viral load, as well as HIV and CD4 specific immunity.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
The study will be based on forty HIV infected patients, receiving anti retroviral treatment (HAART), with CD4 levels between 150-350 and HIV plasma viral load < 5000, for at least 12 months and despite continuous anti-retroviral treatment.
The patients will be randomly divided into two groups, one that will get the T cell vaccination, and the other that will serve as controls.
The T cell vaccine will be prepared from autologous T cells that responded by specific proliferation to recombinant CD4, further expanded in vitro by IL-2, and then fixed by glutaraldehyde.
Each vaccine portion will consist of 10,000 such cells suspended in saline and given subcutaneously every three months during the first year of the trial.
The outcome measures will be CD4 levels, specific immunity to HIV antigens, immune activation profile and HIV plasma viral loads, determined sequentially during the 24 months of the trial.
These outcome measures will be compared between the experimental and the control groups, to determine if this mode of treatment is effective in influencing CD4 levels as an additional mode of treatment during HIV infection.
Undersøgelsestype
Interventionel
Tilmelding (Forventet)
40
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
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Beer Sheba, Israel
- Soroka Medical Center
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-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år til 60 år (Voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months.
- Positive cell proliferation assay to CD4 molecule
- Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months
- No change of antiretroviral treatment for at least 6 months
- Signed informed consent
Exclusion Criteria:
- Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy.
- Pregnancy and women without any efficacious contraception.
- Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl).
- Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min.
- Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Vaccination
One arm of open label T cell vaccination in which all participants will receive the T cell vaccine
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Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.
Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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CD4 T cell levels
Tidsramme: one year follow up
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one year follow up
|
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HIV plasma viral load
Tidsramme: one year follow up
|
one year follow up
|
|
Clinical HIV infection
Tidsramme: one year follow up
|
one year follow up
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
HIV specific immune responses
Tidsramme: One year follow up
|
One year follow up
|
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CD4 specific responses
Tidsramme: One year follow up
|
One year follow up
|
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Immune profile
Tidsramme: One year follow up
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One year follow up
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Studieleder: Klaris Riesenberg, M.D., Soroka U Medical Center
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Abulafia-Lapid R, Bentwich Z, Keren-Zur Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients. J Clin Virol. 2004 Dec;31 Suppl 1:S48-54. doi: 10.1016/j.jcv.2004.09.017.
- Abulafia-Lapid R, Mayan S, Bentwich Z, Keren-Zur Y, Avbramovitz Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients--an extended open trial. Vaccine. 2005 Mar 18;23(17-18):2149-53. doi: 10.1016/j.vaccine.2005.01.054.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. november 2006
Primær færdiggørelse (Faktiske)
1. november 2008
Studieafslutning (Faktiske)
1. november 2008
Datoer for studieregistrering
Først indsendt
3. december 2006
Først indsendt, der opfyldte QC-kriterier
3. december 2006
Først opslået (Skøn)
5. december 2006
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
2. december 2009
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
1. december 2009
Sidst verificeret
1. november 2006
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Patologiske processer
- RNA-virusinfektioner
- Virussygdomme
- Blodbårne infektioner
- Seksuelt overførte sygdomme, virale
- Seksuelt overførte sygdomme
- Lentivirus infektioner
- Retroviridae infektioner
- Immunologiske mangelsyndromer
- Sygdomme i immunsystemet
- Sygdomsegenskaber
- Langsomme virussygdomme
- HIV-infektioner
- Infektioner
- Overførbare sygdomme
- Erhvervet immundefektsyndrom
Andre undersøgelses-id-numre
- sor444006ctil
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .