Clinical trial NCT00053430: Using the Drug Thalidomide to Stimulate T Cells in HIV-Infected People
Official title: Pharmacologic T Cell Costimulation In HIV Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Immune Modulation
Thalidomide
Immune reconstitution
Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2003-01-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite treatment with anti-HIV drugs, people infected with HIV continue to have problems with their immune systems. This study will evaluate whether the drug thalidomide, which stimulates the immune system's T cells, can improve immune system function in people with HIV.

Detailed description: In patients with chronic HIV infection, HIV replication and abnormalities in immune function persist following treatment with highly active antiretroviral therapy (HAART). Specifically, costimulatory T cell interactions are impaired. The immune modulatory drug thalidomide was recently found to costimulate T cells. Pharmacologic T cell costimulation may compensate for the T cell deficiencies in people with HIV disease and improve immune function. This study will test whether thalidomide treatment enhances HIV and cytomegalovirus (CMV)-specific immunity in patients with HIV and CMV, and will evaluate the effect of thalidomide on HIV replication.

In this study, 40 HIV and CMV infected patients on HAART and 40 HIV uninfected CMV seropositive controls will be randomly assigned to low dose thalidomide or placebo treatment for 28 days. T cell responses and HIV replication and genetic diversification will be assessed.

Eligibility criteria: Inclusion Criteria

* HIV-infected for at least 5 years prior to study entry
* CD4 count of 300/mm3 or above
* Pre-HAART nadir CD4 count of 300/mm3 or less
* CMV infection
* HAART for 12 months prior to study entry
* Same effective HAART regimen for 3 months prior to study entry
* HIV viral load less than 200 copies/ml
* Clinically stable

Exclusion Criteria

* Active opportunistic infection
* Females of childbearing potential

Primary outcomes:
measure: Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT
timeFrame: Through Day 28
measure: Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group
timeFrame: Throughout study
measure: Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS)
timeFrame: Throughout study
measure: Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS
timeFrame: Throughout study
Secondary outcomes:
measure: Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group
timeFrame: Throughout study
measure: Increase in adverse events in the thalidomide treatment group
timeFrame: Throughout study
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
Study officials:
affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine
name: Patrick Haslett, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haslett PA, Hanekom WA, Muller G, Kaplan G. Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro. J Infect Dis. 2003 Mar 15;187(6):946-55. doi: 10.1086/368126. Epub 2003 Mar 6.
citation: Haslett PA, Klausner JD, Makonkawkeyoon S, Moreira A, Metatratip P, Boyle B, Kunachiwa W, Maneekarn N, Vongchan P, Corral LG, Elbeik T, Shen Z, Kaplan G. Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients. AIDS Res Hum Retroviruses. 1999 Sep 1;15(13):1169-79. doi: 10.1089/088922299310269.
citation: Matthews SJ, McCoy C. Thalidomide: a review of approved and investigational uses. Clin Ther. 2003 Feb;25(2):342-95. doi: 10.1016/s0149-2918(03)80085-1.