Clinical trial NCT00287677: Induction and Expansion of T Cell Repertoire Using Growth Hormone and Vaccination in HIV-1 Infected Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Growth Hormone
HIV-1
Vaccination
Thymopoiesis
HIV-specific responses
Treatment Experienced
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Hospital Clinic of Barcelona
name: Hospital General Universitario Gregorio Marañon
name: Carlos III Health Institute
First posted: 2006-02-07
Enrollment: 33
Sex: ALL
Minimum age (years): 25
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 highly active antiretroviral therapy (HAART) regimen.

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.

Eligibility 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

Primary outcomes:
measure: 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).
timeFrame: from 24 weeks post rhGH administration
Secondary outcomes:
measure: The rhGH activates the thymic function.
timeFrame: from one year post rhGH administration
measure: This effect is lasting once the rhGH administration is interrupted.
timeFrame: from at least one year since the last rhGH administration
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
Study officials:
affiliation: IrsiCaixa Foundation-Germans Trias i Pujol Hospital
name: Bonaventura Clotet, PhD
role: STUDY_DIRECTOR
affiliation: Irsicaixa Foundation-Germans Trias i Pujol Hospital
name: Lidia Ruiz, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona
name: Jose Mª Gatell, PhD
role: STUDY_DIRECTOR
affiliation: Irsicaixa Foundation- Germans Trias i Pujol Hospital
name: Margarita Bofill, PhD
role: STUDY_DIRECTOR
References: