Induction and Expansion of T Cell Repertoire Using Growth Hormone and Vaccination in HIV-1 Infected Patients

Condition(s) targeted: HIV Infections

Intervention: recombinant human Growth Hormone (Biological); recombinant human Growth Hormone (Biological); VACCINATION (Biological); VACCINATION (Biological)

Phase: Phase 4

Status: Recruiting

Sponsored by: Germans Trias i Pujol Hospital

Official(s) and/or principal investigator(s):
Bonaventura Clotet, PhD, Study Director, Affiliation: IrsiCaixa Foundation-Germans Trias i Pujol Hospital
Lidia Ruiz, PhD, Principal Investigator, Affiliation: Irsicaixa Foundation-Germans Trias i Pujol Hospital
Jose Mª Gatell, PhD, Study Director, Affiliation: Hospital Clinic de Barcelona
Margarita Bofill, PhD, Study Director, Affiliation: Irsicaixa Foundation- Germans Trias i Pujol Hospital

Overall contact:
Laila Darwich, PhD, Phone: +34 93 465 6374, Ext: 123, Email: ldarwich@irsicaixa.es

Concomitant administration of recombinant human growth hormone (rhGH) may boost the expansion of immune reconstitution and broaden specific T cell responses not achievable by vaccination alone. The main objective of that study is to test the validity of this hypothesis with vaccines which are routinely administered to HIV-1 patients(tetanus toxoid and hepatitis A virus vaccines) in order to, if proven of value, use this strategy of HIV vaccination in the near future. This is a pilot, randomized, clinical open label study aimed to investigate thymic functionality and the HIV-specific responses after administration of rhGH in HIV-1 infected patients in HAART regimen.

Official title: Double Strategy to Induce and Expand the T Cell Repertoire by the Administration of Growth Hormone and Vaccination in HIV-1 Infected Patients

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: Proportion of patients HIV+ that recover the immunospecific responses against tetanus toxoid and Hepatitis A at 24 weeks of rhGH administration (time of treatment interruption).

Secondary outcome:

The rhGH activates the thymic function.

This effect is lasting once the rhGH administration is interrupted.

Detailed description: The purpose of a therapeutic vaccine is to control, induce and expand humoral and cellular immune responses capable to control HIV infection. The administration of a conventional vaccine results in the expansion of peripheral clones. Concomitant administration of rhGH may boost this expansion and reconstitute specific T cell responses not achievable by vaccination alone. In this study we want to investigate whether the administration of rhGH expand T cell repertoire and whether there is an increase in the specific cellular responses to HIV-1 and recall antigens and, lately, whether this responses can be further amplified after immunization with tetanus toxoid and hepatitis A vaccines. This Hypothesis will be evaluated by the measurement of thymic volume, the expansion of naïve, memory and effector cell subsets, analysis of thymic emigrants (TRECs)before, during and after rhGH administration and vaccination. Moreover, T cell receptor rearrangement, specific antibodies and cellular responses to antigenic peptides will be determined.

Minimum age: 25 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. HIV-1 asymptomatic patients in HAART regimen (>6 months)

2. Viral load <50 copies/ml

3. Number CD4 cells > 250 cells/mm3

4. Non responders to vaccination (tetanus toxoid and/or Hepatitis A virus)

5. Well-disposition to rhGh daily administration (6 months of treatment)

Exclusion Criteria:

1. AIDS outbreak

2. Allergy or hyperreactivity to rhGH or vaccines

3. Diabetes Mellitus

4. Renal, hepatic, pancreatic disorders

5. Chronic diseases

6. Dementia

7. Pregnancy

Laila Darwich, PhD, Phone: +34 93 465 6374, Ext: 123, Email: ldarwich@irsicaixa.es

Hospital Clinic de Barcelona, Barcelona 08036, Spain; Recruiting
Felipe Garcia, MD, Principal Investigator
Montserrat Plana, PhD, Sub-Investigator

Germans Trias i Pujol Hospital, Badalona, Barcelona 08916, Spain; Recruiting
Laila Darwich, PhD, Principal Investigator
Joan Romeu, MD, Sub-Investigator

Starting date: January 2006
Ending date: September 2008
Last updated: November 14, 2007