Using the Drug Thalidomide to Stimulate T Cells in HIV-Infected People

HIV Infections Clinical Trial

Official title:

Pharmacologic T Cell Costimulation In HIV Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00053430
• Other study ID #: 1R01AI047742-01A1
• Secondary ID: 7R01AI047742-02
• Status: Completed
• Phase: Phase 2
• First received: January 29, 2003
• Last updated: August 6, 2009
• Start date: April 2001
• Est. completion date: February 2006

Study information

• Verified date: August 2009
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2006
• Est. primary completion date: August 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Thalidomide
Tablet taken orally daily
• Thalidomide placebo
Placebo tablet taken orally daily

Locations

Country	Name	City	State
United States	University of Miami School of Medicine	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2003 Mar 6. — View 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. — View Citation

Matthews SJ, McCoy C. Thalidomide: a review of approved and investigational uses. Clin Ther. 2003 Feb;25(2):342-95. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT		Through Day 28	No
Primary	Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group		Throughout study	No
Primary	Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS)		Throughout study	No
Primary	Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS		Throughout study	No
Secondary	Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group		Throughout study	No
Secondary	Increase in adverse events in the thalidomide treatment group		Throughout study	Yes