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

• ClinicalTrials.gov Identifier: NCT00287677
• Recruitment Status: Completed
• First Posted: February 7, 2006
• Last Update Posted: November 4, 2009
• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Hospital Clinic of Barcelona; Hospital General Universitario Gregorio Marañon; Carlos III Health Institute
• Information provided by: Germans Trias i Pujol Hospital

Tracking Information

• First Submitted Date: February 6, 2006
• First Posted Date: February 7, 2006
• Last Update Posted Date: November 4, 2009
• Study Start Date: January 2006
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2007): 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). [ Time Frame: from 24 weeks post rhGH administration ]
• Original Primary Outcome Measures (submitted: February 6, 2006): 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).

Current Secondary Outcome Measures (submitted: November 14, 2007)

• The rhGH activates the thymic function. [ Time Frame: from one year post rhGH administration ]
• This effect is lasting once the rhGH administration is interrupted. [ Time Frame: from at least one year since the last rhGH administration ]

Original Secondary Outcome Measures (submitted: February 6, 2006)

• The rhGH activates the thymic function.
• The effect of the rhGh can be expanded by vaccine immunization.
• This effect is lasting once the rhGH administration is interrupted.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

• Biological: recombinant human Growth Hormone
  Growth Hormone during 6 months (30UG/KG/DAY)
• Biological: Vaccination
  Vaccination (Hepatitis A+B + tetanus toxoid) at week 16
• Drug: HAART
  HAART all over the trial

Study Arms

• Experimental: A
  growth hormone + vaccination + HAART
  Interventions:

  • Biological: recombinant human Growth Hormone
  • Biological: Vaccination
  • Drug: HAART
• Experimental: B
  growth hormone + HAART
  Interventions:

  • Biological: recombinant human Growth Hormone
  • Drug: HAART
• Experimental: C
  vaccination + HAART
  Interventions:

  • Biological: Vaccination
  • Drug: HAART
• Active Comparator: D
  control healthy HIV negative + vaccination
  Intervention: Biological: Vaccination

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2009): 33
• Original Enrollment (submitted: February 6, 2006): 46
• Actual Study Completion Date: July 2009
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 25 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT00287677
• Other Study ID Numbers: VIHCREC01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Germans Trias i Pujol Hospital
• Original Responsible Party: Not Provided
• Current Study Sponsor: Germans Trias i Pujol Hospital
• Original Study Sponsor: Same as current

Collaborators

• Hospital Clinic of Barcelona
• Hospital General Universitario Gregorio Marañon
• Carlos III Health Institute

Investigators

• Study Director: Bonaventura Clotet, PhD; IrsiCaixa Foundation-Germans Trias i Pujol Hospital
• Principal Investigator: Lidia Ruiz, PhD; Irsicaixa Foundation-Germans Trias i Pujol Hospital
• Study Director: Jose Mª Gatell, PhD; Hospital Clinic of Barcelona
• Study Director: Margarita Bofill, PhD; Irsicaixa Foundation- Germans Trias i Pujol Hospital

• PRS Account: Germans Trias i Pujol Hospital
• Verification Date: November 2009