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

Pharmacologic T Cell Costimulation In HIV Disease

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Thalidomide; Drug: Thalidomide placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33125
      • University of Miami School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Participants will receive low dose thalidomide for 28 days	Drug: Thalidomide; Tablet taken orally daily
Placebo Comparator: 2; Participants will receive low dose thalidomide placebo for 28 days	Drug: Thalidomide placebo; Placebo tablet taken orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT	Through Day 28
Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group	Throughout study
Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS)	Throughout study
Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS	Throughout study

Secondary Outcome Measures

Outcome Measure	Time Frame
Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group	Throughout study
Increase in adverse events in the thalidomide treatment group	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Patrick Haslett, MD, Department of Microbiology and Immunology, University of Miami School of Medicine

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): August 1, 2005
• Study Completion (Actual): February 1, 2006

Study Registration Dates

• First Submitted: January 29, 2003
• First Submitted That Met QC Criteria: January 29, 2003
• First Posted (Estimate): January 30, 2003

Study Record Updates

• Last Update Posted (Estimate): August 7, 2009
• Last Update Submitted That Met QC Criteria: August 6, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: Thalidomide; Treatment Experienced; Immune Modulation; Immune reconstitution
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: 1R01AI047742-01A1 (U.S. NIH Grant/Contract); 7R01AI047742-02 (U.S. NIH Grant/Contract)