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

NCT00000973 | Completed Phase 1

• 2 other identifiers: ACTG 10211077
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

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.

Conditions

Toxoplasmosis, Cerebral; HIV Infections

Keywords

Toxoplasmosis; Toxoplasma; Pyrimethamine; Leucovorin; Drug Evaluation; Encephalitis; Zidovudine

Interventions

Pyrimethamine DRUG

Leucovorin calcium DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Glaxo Wellcome: collaborator

Study Sites (2)

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, 10021, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• 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.

  PMID: 8726001 BACKGROUND

MeSH Terms

Conditions

Toxoplasmosis, Cerebral; HIV Infections; Toxoplasmosis; Encephalitis

Interventions

Pyrimethamine; Leucovorin; Zidovudine

Condition Hierarchy (Ancestors)

Brain Abscess; Central Nervous System Infections; Infections; Central Nervous System Protozoal Infections; Central Nervous System Parasitic Infections; Parasitic Diseases; Coccidiosis; Protozoan Infections; Abscess; Suppuration; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Thymidine; Pyrimidine Nucleosides; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• B Luft

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: March 1, 1995
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (2)