Growth Hormone to Increase Immune Function in People With HIV

• ClinicalTrials.gov Identifier: NCT00071240
• Recruitment Status: Completed
• First Posted: October 17, 2003
• Last Update Posted: August 17, 2009
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: The J. David Gladstone Institutes; University of California, San Francisco; National Center for Research Resources (NCRR); EMD Serono
• Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

• First Submitted Date: October 16, 2003
• First Posted Date: October 17, 2003
• Last Update Posted Date: August 17, 2009
• Study Start Date: October 2002
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2008)

• 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 ]
• TREC content in circulating lymphocytes [ Time Frame: Months 0,1,3,6,9,12 ]

Original Primary Outcome Measures (submitted: June 23, 2005)

• Thymus density and size
• percentage and absolute count of naive T cells
• percentage and absolute count of total CD4+ T cells

Current Secondary Outcome Measures (submitted: May 28, 2008)

• 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 ]
• metabolic activity of thymus [ Time Frame: Months 0, 12 ]
• body composition [ Time Frame: Months 0,3,6,12 ]

Original Secondary Outcome Measures (submitted: June 23, 2005)

• Frequency of T cell receptor excision circles (TRECs) in naive T cells
• response of T cells to HIV and cytomegalovirus (CMV)

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

Descriptive Information

• Brief Title: Growth Hormone to Increase Immune Function in People With HIV
• Official Title: The Use of Recombinant Growth Hormone to Enhance T-Cell Production in Adults Infected With HIV-1

Brief Summary

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.

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections

Intervention

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

Study Arms

• Experimental: Growth Hormone Arm
  Growth hormone receipt in the first year, post-growth hormone follow-up in the second year
  Intervention: Drug: Somatropin (recombinant human growth hormone)
• Active Comparator: 2
  Observation only in the 1st year, GH receipt in the second year
  Intervention: Drug: Somatropin (recombinant human growth hormone)

Publications *

• Napolitano LA, Lo JC, Gotway MB, Mulligan K, Barbour JD, Schmidt D, Grant RM, Halvorsen RA, Schambelan M, McCune JM. Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone. AIDS. 2002 May 24;16(8):1103-11. doi: 10.1097/00002030-200205240-00003.
• Napolitano LA, Schmidt D, Gotway MB, Ameli N, Filbert EL, Ng MM, Clor JL, Epling L, Sinclair E, Baum PD, Li K, Killian ML, Bacchetti P, McCune JM. Growth hormone enhances thymic function in HIV-1-infected adults. J Clin Invest. 2008 Mar;118(3):1085-98. doi: 10.1172/JCI32830.
• Tesselaar K, Miedema F. Growth hormone resurrects adult human thymus during HIV-1 infection. J Clin Invest. 2008 Mar;118(3):844-7. doi: 10.1172/JCI35112.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 28, 2008): 22
• Original Enrollment (submitted: June 23, 2005): 24
• Actual Study Completion Date: September 2007
• Actual Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00071240
• Other Study ID Numbers: R01AI043864( U.S. NIH Grant/Contract ); R01AI043864 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Laura A. Napolitano, M.D., Assistant Professor of Medicine, UCSF, Gladstone Institute of Virology and Immunology, UCSF
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Original Study Sponsor: Same as current

Collaborators

• The J. David Gladstone Institutes
• University of California, San Francisco
• National Center for Research Resources (NCRR)
• 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

• PRS Account: National Institute of Allergy and Infectious Diseases (NIAID)
• Verification Date: August 2009