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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pentoxifylline
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Pentoxifylline, Virus Replication, Tumor Necrosis Factor, Drug Evaluation, Acquired Immunodeficiency Syndrome, Cachexia, Drug Synergism

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Beth Israel Deaconess - East Campus A0102 CRS
  • Case CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoechst Marion Roussel
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1. Study Identification

Unique Protocol Identification Number
NCT00000646
Brief Title
Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS
Official Title
Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 1993 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoechst Marion Roussel

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Pentoxifylline, Virus Replication, Tumor Necrosis Factor, Drug Evaluation, Acquired Immunodeficiency Syndrome, Cachexia, Drug Synergism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
54 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pentoxifylline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dezube B
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Crumpacker C
Official's Role
Study Chair
Facility Information:
Facility Name
Beth Israel Deaconess - East Campus A0102 CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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)
Results Reference
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PubMed Identifier
8099612
Citation
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.
Results Reference
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Citation
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)
Results Reference
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PubMed Identifier
7769305
Citation
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.
Results Reference
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PubMed Identifier
1403638
Citation
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.
Results Reference
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Pentoxifylline (Trental) as a Modulator of Tumor Necrosis Factor and of HIV Replication in Patients With AIDS

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