Clinical trial NCT00004276: Phase II Placebo Controlled Study of Thalidomide in Patients With Mycobacterial and HIV Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Mycobacterium Infections
Tuberculosis
Keywords: bacterial infection
human immunodeficiency virus infection
immunologic disorders and infectious disorders
mycobacterium infection
mycobacterium tuberculosis infection
rare disease
viral infection
Lead sponsor: Office of Rare Diseases (ORD)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Rockefeller University
First posted: 1999-10-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: OBJECTIVES: I. Evaluate whether thalidomide modulates toxic host inflammatory responses in patients receiving antitubercular therapy.

II. Evaluate whether thalidomide modifies tumor necrosis factor-mediated toxic symptoms of HIV and mycobacterial infections, and limits progression of HIV immunodeficiency.

III. Evaluate whether thalidomide stimulates immunity in patients with HIV and/or mycobacterial infections.

Detailed description: PROTOCOL OUTLINE: This is a randomized, double blind study. Patients are stratified by type of infection.

Patients are randomly assigned to oral thalidomide or placebo. Therapy is administered daily for up to 8 weeks, beginning the night before antitubercular treatment is initiated.

Eligibility criteria: PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Human immunodeficiency virus (HIV) or mycobacterial infection that requires at least 10 days of inpatient antitubercular treatment

Mycobacterial infection confirmed by positive acid-fast bacilli smear or culture for Mycobacterium tuberculosis

At least 1 of the following signs and symptoms required:

* Temperature over 38 degrees C on at least 2 occasions within 1 week prior to treatment
* Weight loss greater than 5 kg
* Pulmonary involvement in at least 1 lobe on x-ray

Night sweats on at least 2 occasions within 1 week prior to treatment

--Prior/Concurrent Therapy--

Concurrent rifampicin, isoniazid, pyrazinamide, and ethambutol for tuberculosis allowed

--Patient Characteristics--

* No neuropathy and not at risk for neuropathy
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 4 weeks after study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Rockefeller University
name: Gilla Kaplan
role: STUDY_CHAIR
References:
citation: Haslett P, Tramontana J, Burroughs M, Hempstead M, Kaplan G. Adverse reactions to thalidomide in patients infected with human immunodeficiency virus. Clin Infect Dis. 1997 Jun;24(6):1223-7. doi: 10.1086/513665.
citation: Tramontana JM, Utaipat U, Molloy A, Akarasewi P, Burroughs M, Makonkawkeyoon S, Johnson B, Klausner JD, Rom W, Kaplan G. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol Med. 1995 May;1(4):384-97.
citation: Haslett P, Hempstead M, Seidman C, Diakun J, Vasquez D, Freedman VH, Kaplan G. The metabolic and immunologic effects of short-term thalidomide treatment of patients infected with the human immunodeficiency virus. AIDS Res Hum Retroviruses. 1997 Aug 10;13(12):1047-54. doi: 10.1089/aid.1997.13.1047.
citation: Bekker LG, Haslett P, Maartens G, Steyn L, Kaplan G. Thalidomide-induced antigen-specific immune stimulation in patients with human immunodeficiency virus type 1 and tuberculosis. J Infect Dis. 2000 Mar;181(3):954-65. doi: 10.1086/315328.
citation: Klausner JD, Makonkawkeyoon S, Akarasewi P, Nakata K, Kasinrerk W, Corral L, Dewar RL, Lane HC, Freedman VH, Kaplan G. The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Mar 1;11(3):247-57. doi: 10.1097/00042560-199603010-00005.