Efficacy Study of T Cell Vaccination in HIV Infection

This study has been completed.
Sponsor:
Information provided by:
Soroka University Medical Center
ClinicalTrials.gov Identifier:
NCT00407836
First received: December 3, 2006
Last updated: December 1, 2009
Last verified: November 2006
  Purpose

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.


Condition Intervention Phase
HIV Infections
Biological: T cell vaccination
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection

Resource links provided by NLM:


Further study details as provided by Soroka University Medical Center:

Primary Outcome Measures:
  • CD4 T cell levels [ Time Frame: one year follow up ] [ Designated as safety issue: No ]
  • HIV plasma viral load [ Time Frame: one year follow up ] [ Designated as safety issue: No ]
  • Clinical HIV infection [ Time Frame: one year follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • HIV specific immune responses [ Time Frame: One year follow up ] [ Designated as safety issue: No ]
  • CD4 specific responses [ Time Frame: One year follow up ] [ Designated as safety issue: No ]
  • Immune profile [ Time Frame: One year follow up ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: November 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccination
One arm of open label T cell vaccination in which all participants will receive the T cell vaccine
Biological: T cell vaccination
Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.
Biological: T cell vaccination
Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months.
  2. Positive cell proliferation assay to CD4 molecule
  3. Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months
  4. No change of antiretroviral treatment for at least 6 months
  5. Signed informed consent

Exclusion Criteria:

  1. Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy.
  2. Pregnancy and women without any efficacious contraception.
  3. Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl).
  4. Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min.
  5. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00407836

Locations
Israel
Soroka Medical Center
Beer Sheba, Israel
Sponsors and Collaborators
Soroka University Medical Center
Investigators
Study Director: Klaris Riesenberg, M.D. Soroka U Medical Center
  More Information

Publications:
Responsible Party: Zvi Bentwich, M.D, Ben Gurion University of the Negev
ClinicalTrials.gov Identifier: NCT00407836     History of Changes
Other Study ID Numbers: sor444006ctil
Study First Received: December 3, 2006
Last Updated: December 1, 2009
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Soroka University Medical Center:
HIV
CD4 T cell level
CD4 autoimmunity
Viral load
T cell vaccination
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 31, 2014