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A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients
This study has been completed.
First Received: November 2, 1999   Last Updated: July 31, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator: Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000973
  Purpose

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.


Condition Intervention Phase
Toxoplasmosis, Cerebral
HIV Infections
Drug: Pyrimethamine
Drug: Leucovorin calcium
Drug: Zidovudine
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 26
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000973

Locations
United States, California
Palo Alto Veterans Adm Med Ctr / Stanford Univ
Palo Alto, California, United States, 94304
United States, New York
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: B Luft
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG 102
Study First Received: November 2, 1999
Last Updated: July 31, 2008
ClinicalTrials.gov Identifier: NCT00000973     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Toxoplasmosis
Toxoplasma
Pyrimethamine
Leucovorin
Drug Evaluation
Encephalitis
Zidovudine

Additional relevant MeSH terms:
Communicable Diseases
Anti-Infective Agents
Antiprotozoal Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Brain Diseases
Antimalarials
Antiparasitic Agents
Therapeutic Uses
Suppuration
Nucleic Acid Synthesis Inhibitors
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Brain Abscess
Toxoplasmosis
Virus Diseases
HIV Infections
Pyrimethamine
Antimetabolites
Sexually Transmitted Diseases, Viral
Toxoplasmosis, Cerebral
Leucovorin
Zidovudine
Infection
Central Nervous System Parasitic Infections
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on November 09, 2009