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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00053430

Purpose

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.

Condition	Intervention	Phase
HIV Infections	Drug: Thalidomide Drug: Thalidomide placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Treatment
Official Title:	Pharmacologic T Cell Costimulation In HIV Disease

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Thalidomide

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Doubling in HIV Pol-specific CD8 cells, measured by ELISPOT [ Time Frame: Through Day 28 ] [ Designated as safety issue: No ]
Increase in CMV pp65 CD8 cells, measured by ELISPOT in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Increase in HIV p24-specific IFN-gamma-secreting CD4 cells in the thalidomide treatment group, measured by fluorescence-activated cell sorting (FACS) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Increase in cytomegalovirus (CMV)-specific interferon (IFN)-gamma-secreting CD4 T cells in the thalidomide treatment group, measured by FACS [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Increase in the frequency of keyhole limpet hemocyanin (KLH)-specific lymphocyte proliferative responses in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Increase in adverse events in the thalidomide treatment group [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Enrollment:	40
Study Start Date:	April 2001
Study Completion Date:	February 2006
Primary Completion Date:	August 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00053430

Locations

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

Sponsors and Collaborators

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

More Information

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. 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.

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

Responsible Party:	Rona Siskind, DAIDS
ClinicalTrials.gov Identifier:	NCT00053430 History of Changes
Other Study ID Numbers:	1R01AI47742-01A1, 7R01AI047742-02
Study First Received:	January 29, 2003
Last Updated:	August 6, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Immune Modulation
Thalidomide
Immune reconstitution
Treatment Experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Thalidomide
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 09, 2012