Growth Hormone to Increase Immune Function in People With HIV

This study has been completed.
Sponsor:
Collaborators:
The J. David Gladstone Institutes
University of California, San Francisco
EMD Serono
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00071240
First received: October 16, 2003
Last updated: August 14, 2009
Last verified: August 2009
  Purpose

Growth hormone plays an important role in the development of the immune system. Studies suggest that growth hormone may promote growth of the thymus, a gland responsible for the production of important immune cells called T cells. Since these cells are lost during the course of HIV infection, it is possible that growth hormone treatment could help restore the immune system. This study will determine whether the administration of growth hormone can increase the size and function of the thymus and cause an increase in the number of new T cells in the blood of people infected with HIV.

Study hypothesis: Growth hormone treatment will enhance T cell production in HIV infected adults.


Condition Intervention Phase
HIV Infections
Drug: Somatropin (recombinant human growth hormone)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Use of Recombinant Growth Hormone to Enhance T-Cell Production in Adults Infected With HIV-1

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Effect of 1 year of growth hormone treatment on thymus mass, naive and total T cells [ Time Frame: Thymus mass- months 0,6,12; Naive and total T cells - months 1,3,6,9,12 ] [ Designated as safety issue: No ]
  • TREC content in circulating lymphocytes [ Time Frame: Months 0,1,3,6,9,12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of 1 year of growth hormone treatment on B cells, NK cells, CD34+ cells, activated T cells, circulating IGF-1 levels, circulating cytokine levels, T cell function and repertoire [ Time Frame: T cell repertoire Months 0,6,12, all others Months 0,1,3,6,9,12 ] [ Designated as safety issue: No ]
  • metabolic activity of thymus [ Time Frame: Months 0, 12 ] [ Designated as safety issue: No ]
  • body composition [ Time Frame: Months 0,3,6,12 ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: October 2002
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Growth Hormone Arm
Growth hormone receipt in the first year, post-growth hormone follow-up in the second year
Drug: Somatropin (recombinant human growth hormone)
3.0mg sc daily for 6 months, followed by 1.5mg sc daily for 6 months. Dose stopped, held or reduced by study investigators as indicated by adverse events
Other Name: Serostim
Active Comparator: 2
Observation only in the 1st year, GH receipt in the second year
Drug: Somatropin (recombinant human growth hormone)
3.0mg sc daily for 6 months, followed by 1.5mg sc daily for 6 months. Dose stopped, held or reduced by study investigators as indicated by adverse events
Other Name: Serostim

Detailed Description:

The thymus is the major organ of T cell production and is generally believed to be nonfunctional in adults. Even if nonfunctional, it is destroyed by HIV infection while T cells are destroyed in the peripheral lymphoid system. Given the absence of new T cell production and a pathologic acceleration of T cell destruction, the immune system collapses and immunodeficiency ensues.

However, some studies have demonstrated thymic function in adults with HIV disease. Such function may be induced by positive feedback regulation of T cell production and the presence or absence of such function may play a determinant role in disease progression and response to highly active antiretroviral therapy (HAART). These studies suggest that the thymus is functional in many adults with HIV disease and that thymic function might be induced as a consequence of HIV-mediated peripheral T cell depletion. Growth hormone is a potent regulator of thymic function. This study will determine whether true thymic function can be induced in HIV infected adults, whether such induction is indeed prompted by growth hormone, and whether thymic function plays a role in sustaining the T cell compartment in the face of peripheral T cell depletion.

Twenty-four volunteers will be enrolled in this 2 year study. All participants will receive 12 months of treatment with human growth hormone. Participants will be randomly assigned to one of two study arms. Twelve participants (Arm 1) will receive growth hormone during the first year of the study (3 mg given daily by subcutaneous injection, with dose reduction to 1.5 mg after 6 months). Twelve participants (Arm 2) will be enrolled in an observational control arm (no placebo injections) that will cross over to growth hormone treatment after 1 year. Participants, whether in Arm 1 or Arm 2, will have as many as 24 scheduled study visits during the 2 years after enrollment. In general, study visits occur every every 1 to 3 months. Study visits will include physical exams, blood tests, CT scans, PET scans, and DEXA scans.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV infected
  • CD4 count 400 cells/mm3 or less
  • HIV viral load less than 1000 copies/ml for 1 year prior to study entry; in some cases, viral load up to 5000 copies/ml will be acceptable
  • Taking at least 2 anti-HIV medications

Exclusion Criteria:

  • Diabetes
  • Cancer. Patients with some cases of Kaposi's sarcoma or skin cancer will not be excluded.
  • Some (not all) forms of heart disease
  • Carpal Tunnel Syndrome
  • Pregnant or breastfeeding
  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: NCT00071240

Locations
United States, California
Gladstone Institute of Virology and Immunology
San Francisco, California, United States, 94141
Sponsors and Collaborators
The J. David Gladstone Institutes
University of California, San Francisco
EMD Serono
Investigators
Principal Investigator: Laura A. Napolitano, MD University of California, San Francisco
Principal Investigator: Joseph M. McCune, MD, PhD University of California, San Francisco
  More Information

Publications:
Responsible Party: Laura A. Napolitano, M.D., Assistant Professor of Medicine, UCSF, Gladstone Institute of Virology and Immunology, UCSF
ClinicalTrials.gov Identifier: NCT00071240     History of Changes
Other Study ID Numbers: R01AI43864, R01 AI43864
Study First Received: October 16, 2003
Last Updated: August 14, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Growth Hormone
HIV
AIDS
Thymus
CD4 Cell
Immune System
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014