Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS

NCT ID: NCT00000646

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1993-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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Pentoxifylline Virus Replication Tumor Necrosis Factor Drug Evaluation Acquired Immunodeficiency Syndrome Cachexia Drug Synergism

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Pentoxifylline

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoechst Marion Roussel

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dezube B

Role: STUDY_CHAIR

Crumpacker C

Role: STUDY_CHAIR

Locations

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Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

Countries

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United States

References

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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)

Reference Type BACKGROUND

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 (1988). 1993 Jul;6(7):787-94.

Reference Type BACKGROUND
PMID: 8099612 (View on PubMed)

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)

Reference Type BACKGROUND

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. doi: 10.1093/infdis/171.6.1628.

Reference Type BACKGROUND
PMID: 7769305 (View on PubMed)

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 (1988). 1992;5(11):1099-104.

Reference Type BACKGROUND
PMID: 1403638 (View on PubMed)

Other Identifiers

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11135

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 160

Identifier Type: -

Identifier Source: org_study_id