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A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00000812
First Posted: August 31, 2001
Last Update Posted: April 4, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose

PRIMARY: To evaluate the safety, tolerability, and pharmacokinetics of daily oral thalidomide.

SECONDARY: To examine the effect of thalidomide on antiviral activity and tumor necrosis factor-alpha (TNF-alpha) production, and the correlation between TNF-alpha inhibition and viral burden.

A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.


Condition Intervention Phase
HIV Infections Drug: Thalidomide Phase 1

Study Type: Interventional
Study Design: Masking: Double
Primary Purpose: Treatment
Official Title: A Phase I, Placebo-Controlled, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Thalidomide in Subjects With HIV-1 Infection

Resource links provided by NLM:


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

Estimated Enrollment: 36
Study Completion Date: July 2000
Detailed Description:

A protein in the blood called tumor necrosis factor (TNF-alpha) is abnormally elevated in patients with HIV infection and may cause the body to produce more virus. In vitro studies have demonstrated that thalidomide reduces TNF-alpha levels and inhibits production of HIV. However, more information on the pharmacological and immunological aspects of thalidomide is needed.

Patients are randomized to receive oral thalidomide or matching placebo (3:1) at one of three dose levels daily for 8 weeks. All 12 patients at a dose level must receive treatment for at least 2 weeks before dose escalation in subsequent patients occurs. The MTD is defined as the dose level immediately below that at which 3 or more of 9 patients receiving thalidomide experience dose-limiting toxicity. Patients are followed for a total of 16 weeks.

PER 6/20/95 AMENDMENT: Patients in cohort 1 should discontinue the previous 50 mg formulation of thalidomide once the new formulation is available. Those patients may either wash out for 4 weeks and recommence the study or discontinue the study.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed for occasional use (chronic use is permitted only if clinician deems that medication can be discontinued in the event of overlapping toxicity):

  • CNS active agents, such as alcohol, narcotics (i.e., morphine, codeine, meperidine), barbiturates, benzodiazepines, tricyclic antidepressants, phenothiazines, sedating antihistamines, or over-the-counter sleeping aids.

Patients must have:

  • HIV infection.
  • CD4 count 200 - 500 cells/mm3.
  • No active opportunistic infection requiring systemic therapy within the past 14 days.
  • NOTE: Women must be post-menopausal or provide written documentation of surgical sterilization, and sexually active men must use a barrier method of contraception, beginning 4 weeks prior to study entry and continuing until 4 weeks following end of treatment.

PER AMENDMENT 8/2/96:

  • Been on stable licensed antiretroviral treatment for 60 days prior to study entry or must not have received any antiretroviral medications for 60 days prior to study entry.

Prior Medication:

Required:

  • Patients must have been on stable licensed antiretroviral treatment for 60 days prior to study entry or must not have received any antiretroviral medications for 60 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy requiring chemotherapy.
  • Grade 2 or worse peripheral neuropathy.
  • Medical condition that would interfere with evaluation of patient.

Concurrent Medication:

Excluded in all patients:

  • Didanosine ( ddI ).
  • Zalcitabine ( ddC ).
  • Stavudine ( d4T ).
  • Other immunologically active agents.
  • Systemic cytotoxic chemotherapy.

Excluded in all patients unless taken only occasionally or unless medication could be stopped in the event of overlapping toxicity:

  • CNS active agents, such as alcohol, narcotics (i.e., morphine, codeine, meperidine), barbiturates, benzodiazepines, tricyclic antidepressants, phenothiazines, sedating antihistamines, or over-the-counter sleeping aids.

Patients with the following prior conditions are excluded:

  • History of active tuberculosis within 3 months prior to study entry.
  • History of intolerance to thalidomide such as fever, rash, or neuropathy.

Prior Medication:

Excluded within 14 days prior to study entry:

  • Systemic chemotherapy.

Excluded within 30 days prior to study entry:

  • Topical, oral, and systemic corticosteroids.
  • Pentoxifylline.
  • Interferons.
  • Interleukins.
  • Cimetidines.
  • Acetylcysteine or other glutathione depleting agents.
  • Other putative immunomodulatory agents such as thymosin alpha 1, thymopentin, isoprinosine, ditiocarb sodium, ampligen, and immune globulin.

PER AMENDMENT 8/2/96:

Excluded within 60 days prior to study entry:

  • Therapy with investigational antiretroviral medications.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000812


Locations
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, New York
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Celgene Corporation
Investigators
Study Chair: Teppler H
Study Chair: Pomerantz R
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000812     History of Changes
Other Study ID Numbers: ACTG 267
42,240
11243 ( Registry Identifier: DAIDS-ES )
First Submitted: November 2, 1999
First Posted: August 31, 2001
Last Update Posted: April 4, 2012
Last Verified: April 2012

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Thalidomide

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents