Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Pentoxifylline (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Dezube B, Study Chair
Crumpacker C, Study Chair
Summary
To determine whether pentoxifylline lowers tumor necrosis factor (TNF) levels in AIDS
patients. Pentoxifylline decreases tumor necrosis factor (TNF), and therefore should decrease
such TNF-intensified events as cachexia, enhanced HIV expression, and inhibition of
zidovudine (AZT) activity.
Clinical Details
Official title: Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS
Study design: Treatment
Detailed description:
Pentoxifylline decreases tumor necrosis factor (TNF), and therefore should decrease such
TNF-intensified events as cachexia, enhanced HIV expression, and inhibition of zidovudine
(AZT) activity.
Twenty-seven AIDS patients with elevated TNF and less than 300 CD4 cells are given
pentoxifylline 3 times a day for 8 weeks. If no significant changes are seen in virologic,
immunologic, or related measures, 27 additional patients are given a higher dose of
pentoxifylline 3 times a day for eight weeks.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
Concurrent Medication:
Required:
- Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), or a combination thereof,
at current dosage for the 8 weeks of study treatment.
- Prophylaxis (e. g., aerosolized pentamidine, trimethoprim / sulfamethoxazole (TMP /
SMX), dapsone for Pneumocystis carinii pneumonia (PCP) if CD4 cell count is < 200
cells/mm3
Allowed:
- Concurrent maintenance therapy for opportunistic infections.
Prior Medication: Required:
- Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), or a combination thereof,
for at least 2 months.
Patients must have the following:
- Diagnosis of AIDS.
- Documented HIV seropositivity.
- Ability to give informed consent and willingness to comply with visit schedule and all
procedures.
Exclusion Criteria
Co-existing Condition:
Patients with the following conditions or symptoms are excluded:
- Lymphoma or visceral Kaposi's sarcoma.
- Active peptic ulcer or bleeding disorder.
- Hemophilia. Known intolerance to pentoxifylline, theophylline, or caffeine.
Concurrent Medication:
Excluded:
- Warfarin and heparin.
- Biological response modifiers (e. g., erythropoietin, interferon, G-CSF, GM-CSF).
Cytotoxic chemotherapy.
- Megestrol acetate. Corticosteroids.
Concurrent Treatment:
Excluded:
- Radiation therapy. Blood products or transfusions.
Patients with the following are excluded:
- Presence of an active opportunistic infection.
- Major surgery within 30 days of study treatment.
Prior Medication:
Excluded:
- Biological response modifiers (including interferon, interleukin), corticosteroids, or
megestrol acetate within 14 days of first (screening) TNF level.
- Erythropoietin dependency or within 30 days of study treatment.
Prior Treatment:
Excluded:
- Transfusion or blood product dependency or use within 30 days of study treatment.
Locations and Contacts
Beth Israel Deaconess Med Ctr, Boston, Massachusetts 02215, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Additional Information
Related publications: Dezube BJ, Lederman MM, Pardee AB, Chapman B, Korvick J, Crumpacker CS. Pentoxifylline (Trental, PTX) decreases tumor necrosis factor (TNF) & may decrease HIV replication in AIDS patients. ACTG #160 Team. Int Conf AIDS. 1993 Jun 6-11;9(1):492 (abstract no PO-B28-2142) Dezube BJ, Pardee AB, Chapman B, Beckett LA, Korvick JA, Novick WJ, Chiurco J, Kasdan P, Ahlers CM, Ecto LT, et al. Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. NIAID AIDS Clinical Trials Group. J Acquir Immune Defic Syndr. 1993 Jul;6(7):787-94. Dezube BJ, Pardee AB, Chapman B, Beckett L, Korvick J, Ahlers CM, Ecto L, Chatis P, Crumpacker CS. Pentoxifylline (trental) decreases tumor necrosis factor (TNF) and HIV replication in patients with AIDS. ACTG #160 Team. AIDS Clinical Trial Group. Int Conf AIDS. 1992 Jul 19-24;8(1):Mo8 (abstract no MoB 0019) Dezube BJ, Lederman MM, Spritzler JG, Chapman B, Korvick JA, Flexner C, Dando S, Mattiacci MR, Ahlers CM, Zhang L, et al. High-dose pentoxifylline in patients with AIDS: inhibition of tumor necrosis factor production. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. J Infect Dis. 1995 Jun;171(6):1628-32. Dezube BJ, Pardee AB, Beckett LA, Ahlers CM, Ecto L, Allen-Ryan J, Anisowicz A, Sager R, Crumpacker CS. Cytokine dysregulation in AIDS: in vivo overexpression of mRNA of tumor necrosis factor-alpha and its correlation with that of the inflammatory cytokine GRO. J Acquir Immune Defic Syndr. 1992;5(11):1099-104.
Last updated: June 23, 2005
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