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A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients

Primary Purpose

Toxoplasmosis, Cerebral, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pyrimethamine
Leucovorin calcium
Zidovudine
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 Toxoplasmosis, Cerebral focused on measuring Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Encephalitis, Zidovudine

Eligibility Criteria

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

Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis. Isoniazid not initiated during study period. Methadone maintenance. Required: Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Prior history of toxoplasmic encephalitis. Unable to take oral medication reliably or have a malabsorption syndrome (i.e., 3 or more loose stools/day for at least 4 weeks associated with an unintentional weight loss of = or > 10 percent of body weight). History of sensitivity to the study medications. Concurrent Medication: Excluded: Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy. Medications such as aspirin, benzodiazepines, cimetidine, indomethacin, morphine, and sulfonamides should be avoided. Concurrent Treatment: Excluded: Lymphocyte replacement. Patients with the following are excluded: Any medical or social condition that, in the opinion of the investigator, would adversely affect either participation or compliance in the study. Diagnosis of AIDS and febrile and have evidence of another serious opportunistic infection or central nervous system impairment. Prior Medication: Excluded: Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy within past 14 days. Prior Treatment: Excluded: Lymphocyte replacement within past 14 days. Patients have the following symptoms and conditions: Laboratory evidence of HIV infection. Serological evidence of exposure to Toxoplasma gondii, but no clinical evidence of active toxoplasmic infection. Able to understand and sign a written informed consent. Either homosexual male or intravenous drug user. Required: Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day for 4 weeks. Intravenous drug abuse.

Sites / Locations

  • Memorial Sloan-Kettering Cancer Ctr.
  • Unc Aids Crs

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Glaxo Wellcome
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1. Study Identification

Unique Protocol Identification Number
NCT00000973
Brief Title
A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients
Official Title
Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii
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 1995 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
To determine the manner in which pyrimethamine is metabolized and excreted in patients currently receiving zidovudine (AZT). An important goal of this measurement is to establish the optimal dose of pyrimethamine necessary to prevent the development of toxoplasmosis in AIDS patients or delay the subsequent return of toxoplasmic encephalitis. Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.
Detailed Description
Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine. Patients receive the study treatment for a total of 22 days. Patients are given an initial dose of pyrimethamine followed by a lower dose given as a single oral daily dose for 21 days. Patients continue to receive AZT at the dose prescribed prior to enrollment in the study. Patients receive leucovorin calcium once a day. Neither the leucovorin calcium nor the AZT are provided through the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Toxoplasmosis, Cerebral, HIV Infections
Keywords
Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Encephalitis, Zidovudine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
26 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pyrimethamine
Intervention Type
Drug
Intervention Name(s)
Leucovorin calcium
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis. Isoniazid not initiated during study period. Methadone maintenance. Required: Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Prior history of toxoplasmic encephalitis. Unable to take oral medication reliably or have a malabsorption syndrome (i.e., 3 or more loose stools/day for at least 4 weeks associated with an unintentional weight loss of = or > 10 percent of body weight). History of sensitivity to the study medications. Concurrent Medication: Excluded: Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy. Medications such as aspirin, benzodiazepines, cimetidine, indomethacin, morphine, and sulfonamides should be avoided. Concurrent Treatment: Excluded: Lymphocyte replacement. Patients with the following are excluded: Any medical or social condition that, in the opinion of the investigator, would adversely affect either participation or compliance in the study. Diagnosis of AIDS and febrile and have evidence of another serious opportunistic infection or central nervous system impairment. Prior Medication: Excluded: Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy within past 14 days. Prior Treatment: Excluded: Lymphocyte replacement within past 14 days. Patients have the following symptoms and conditions: Laboratory evidence of HIV infection. Serological evidence of exposure to Toxoplasma gondii, but no clinical evidence of active toxoplasmic infection. Able to understand and sign a written informed consent. Either homosexual male or intravenous drug user. Required: Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day for 4 weeks. Intravenous drug abuse.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
B Luft
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8726001
Citation
Jacobson JM, Davidian M, Rainey PM, Hafner R, Raasch RH, Luft BJ. Pyrimethamine pharmacokinetics in human immunodeficiency virus-positive patients seropositive for Toxoplasma gondii. Antimicrob Agents Chemother. 1996 Jun;40(6):1360-5. doi: 10.1128/AAC.40.6.1360.
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A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients

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