Clinical trial NCT00050921: Administration of Growth Hormone to Increase CD4+ Count in Patients Taking Anti-HIV Drugs
Official title: Improving Immune Reconstitution With Growth Hormone in HIV-infected Subjects With Incomplete CD4+ Lymphocyte Restoration on Highly Active Antiretroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV Infections
CD4 Lymphocyte Count
Antiretroviral Therapy, Highly Active
Growth Hormone
Cell Division
CD4-Positive T-Lymphocytes
Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2003-01-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the ability of growth hormone (GH, also known as somatropin) to increase CD4+ cell counts in patients taking anti-HIV drugs. The study is targeted toward patients with low levels of HIV who continue to have low CD4+ cell counts.

Detailed description: After initiation of HAART, many HIV infected patients have significant improvement in CD4+ levels. However, some patients continue to have low CD4+ counts (\< 350 cells/mm3) despite adequate viral suppression. The purpose of this study is to determine whether administration of GH will increase naïve CD4+ production. Further, the study will assess whether an increase in naïve CD4+ production will lead to increases in antigen-specific CD4+ and CD8+ T cells.

Patients enrolled in this study will be randomized to one of two groups. Patients in both groups will continue their present HAART regimen for the duration of the study. Group A patients will receive daily subcutaneous injections of GH for 48 weeks. Group B participants will receive no additional therapy for 24 weeks, and will then receive daily subcutaneous GH injections during Weeks 24-28 of the study. Both groups will receive immunocyanin (keyhole-limpet hemocyanin) injections at Weeks 16 and 20 and hepatitis A vaccination at Weeks 40 and 44. At the conclusion of Week 48, all patients will discontinue GH therapy while maintaining their HAART regimen. Patients will then be followed for an additional 24 weeks.

Patients may be asked to participate in a substudy to measure the size of the thymus in people taking GH. Patients in the substudy will have a noncontrast CT scan of the chest before beginning GH therapy and again after 24 weeks of GH therapy.

Eligibility criteria: Inclusion Criteria

* HIV positive
* Minimum of 1 year of treatment with HAART
* CD4+ cell count \<350 cells/mm3
* HIV-1 RNA \<400 copies/ml for 6 months prior to study entry
* Acceptable methods of contraception

Exclusion Criteria

* Serious medical illness requiring hospitalization within 14 days prior to study entry
* Pregnant or breast-feeding
* Taking certain medications
* Allergy to r-hGH, hepatitis A vaccine, KLH, or their formulations, including allergies to shellfish
* Active drug or alcohol dependence
* Diabetes or uncontrolled hyperglycemia
* Uncontrolled hypertension
* History of carpal tunnel syndrome
* Active neoplasm requiring treatment

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Univ. of California Davis Med. Ctr., ACTU
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Iowa City
country: United States
facility: Univ. of Iowa Healthcare, Div. of Infectious Diseases
state: Iowa
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Dallas
country: United States
facility: Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic
state: Texas
Study officials:
affiliation: Rush Medical College of Rush University
name: Kimberly Smith, M.D., MPH
role: STUDY_CHAIR
References:
citation: Connick E, Lederman MM, Kotzin BL, Spritzler J, Kuritzkes DR, St Clair M, Sevin AD, Fox L, Chiozzi MH, Leonard JM, Rousseau F, D'Arc Roe J, Martinez A, Kessler H, Landay A. Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response. J Infect Dis. 2000 Jan;181(1):358-63. doi: 10.1086/315171.
citation: Smith KY, Valdez H, Landay A, Spritzler J, Kessler HA, Connick E, Kuritzkes D, Gross B, Francis I, McCune JM, Lederman MM. Thymic size and lymphocyte restoration in patients with human immunodeficiency virus infection after 48 weeks of zidovudine, lamivudine, and ritonavir therapy. J Infect Dis. 2000 Jan;181(1):141-7. doi: 10.1086/315169.
citation: Vigano A, Vella S, Saresella M, Vanzulli A, Bricalli D, Di Fabio S, Ferrante P, Andreotti M, Pirillo M, Dally LG, Clerici M, Principi N. Early immune reconstitution after potent antiretroviral therapy in HIV-infected children correlates with the increase in thymus volume. AIDS. 2000 Feb 18;14(3):251-61. doi: 10.1097/00002030-200002180-00007.
citation: Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, Wang J, Bozzette SA, Breitmeyer JB. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group. Ann Intern Med. 1996 Dec 1;125(11):873-82. doi: 10.7326/0003-4819-125-11-199612010-00002.
citation: 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.