A Study to Evaluate the Ability of TNFR:Fc to Decrease the Amount of IL-6 (Interleukin-6) and TNF-alpha (Tumor Necrosis Factor) in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001116
First received: November 2, 1999
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to determine if TNFR:Fc (a molecule that attaches to TNF) can lower the amount of IL-6 in HIV-positive patients. This study will also examine the effect of TNFR:Fc on TNF-alpha. IL-6 and TNF-alpha are 2 substances produced by the immune system that may increase the rate of HIV replication.

IL-6 and TNF-alpha are produced naturally by the body. High levels of TNF-alpha lead to increased IL-6 production and increased HIV replication, therefore helping the virus infect the body. HIV-positive patients who receive IL-2 (interleukin-2, a protein that helps the immune system fight infection) tend to have higher levels of IL-6 and TNF-alpha than patients not receiving IL-2. These increased levels may contribute to some of the flu-like symptoms related to IL-2 administration. TNFR:Fc can neutralize TNF-alpha to decrease the action of TNF-alpha and, in turn, decrease the amount of IL-6 in the body. TNFR:Fc may, therefore, have a role in the treatment of HIV disease or in relieving some of the symptoms related to IL-2 administration.


Condition Intervention
HIV Infections
Drug: Tumor Necrosis Factor soluble receptor-immunoadhesin complex

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: Effect of Recombinant Human Soluble Tumor Necrosis Factor Receptor (TNFR:Fc) on Interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-alpha) and Markers of Immune Activation in HIV-Infected Subjects

Resource links provided by NLM:


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

Estimated Enrollment: 18
Study Completion Date: June 2000
Detailed Description:

Both Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) are substances naturally produced by the body's immune system. Evidence suggests that TNF-alpha production may be excessive or inappropriate in HIV-infected patients. Elevated TNF-alpha levels can result in increased IL-6 production and possibly increased HIV replication. TNFR:Fc is a modification of a natural substance that binds to TNF-alpha and neutralizes its activity. It is postulated that TNFR:Fc may result in decreased activity of TNF-alpha and lower IL-6 levels. HIV-infected patients who receive Interleukin-2 (IL-2) have been shown to have higher TNF-alpha and IL-6 levels than those who do not receive IL-2. It is thought that these higher levels of TNF-alpha and IL-6 may contribute to some of the flu-like symptoms experienced by patients receiving IL-2. By decreasing the amount of IL-6 in the body and by decreasing the action of TNF-alpha in the body, TNFR:Fc may have a role in the treatment of HIV disease or in alleviating some of the symptoms related to IL-2 administration.

Six patients from each of the 3 treatment arms of ACTG 328 (HAART alone, HAART plus intravenous (IV) rhIL-2, and HAART plus subcutaneous (SC) rhIL-2) who are about to be randomized to Step II of ACTG 328 may participate in this prospective, nested substudy. Patients randomized to the Interleukin-2 (IL-2) arms of ACTG 328 are pretreated with TNFR:Fc (administered by infusion over 30 minutes) at week 16 of ACTG 928 (Course 3, Week 28 of ACTG 328), just prior to initiation of IL-2. Those randomized to the highly active antiretroviral therapy (HAART) only arm of ACTG 328 receive treatment with TNFR:Fc at Week 16 of ACTG 928 (Week 28 of ACTG 328).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

You may be eligible for this study if you:

  • Are HIV-positive.
  • Are enrolled in ACTG 328.
  • Agree to practice abstinence or use barrier methods of birth control during the study.
  • Are at least 18 years old.

Exclusion Criteria

You will not be eligible for this study if you:

  • Have any active opportunistic (HIV-associated) infections.
  • Have any medical condition or psychological issue that would interfere with study requirements.
  • Are pregnant or breast-feeding.
  • Are receiving any experimental drug other than IL-2.
  • Are receiving certain other medications.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001116

Locations
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Study Chair: Sha B
Study Chair: Valdez H
Study Chair: Landay A
Study Chair: Lederman M
  More Information

Publications:
Sha B, Valdez H, Landay A, Gelman R, Namkung A, Agosti J, Bancroft L, Mildvan D, Mitsuyasu R, Pollard R, Ogata-Arakaki D, Kilgo P, Estep S, Fox L, Lederman M. Effect of recombinant human soluble tumor necrosis factor receptor (TNFR, etanercept) on interleukin-6 (IL- 6), TNF-a, and markers of immune activation in HIV-infected subjects receiving interleukin-2 (IL-2). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 66)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001116     History of Changes
Other Study ID Numbers: ACTG 928, 11498
Study First Received: November 2, 1999
Last Updated: May 21, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Tumor Necrosis Factor
Interleukin-2
Immunity, Cellular
Antiviral Agents
Interleukin-6
Receptors, Tumor Necrosis Factor

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Necrosis
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
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2014