Toxoplasmosis, CerebralPhase 1NCT00000973
A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients
A Phase 1 study testing Pyrimethamine, Leucovorin calcium and Zidovudine in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Toxoplasmosis, Cerebral, HIV Infections
- What is being tested?
- Pyrimethamine, Leucovorin calcium and Zidovudine
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- Start not givento Mar 1995
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
Show all 29Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Unc Aids Crs
Chapel Hill, North Carolina, 27599
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, 10021
About this study
Official title: Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii
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.
Read the 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.
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Being tested
- Pyrimethamine, Leucovorin calcium, Zidovudine
- Keywords
- Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Encephalitis, Zidovudine
- Medical subject headings
- Toxoplasmosis, Cerebral, HIV Infections, Toxoplasmosis, Encephalitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyrimethamineDrug
ZidovudineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionMar 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Toxoplasmosis, CerebralStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Masking
- None (open label)
- Enrolment
- 26 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Glaxo Wellcome
- Responsible party
- Sponsor
- Investigators
- B Luft, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000973
- Sponsor's protocol ID
- ACTG 102
- Other IDs
- 11077
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 4 Nov 2021
- Results posted
- No
Publications
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.
PubMed 8726001
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii
- ClinicalTrials.gov ID
- NCT00000973
- Acronym / sponsor ID
- ACTG 102
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Keywords
- Toxoplasmosis, Toxoplasma, Pyrimethamine, Leucovorin, Drug Evaluation, Encephalitis, Zidovudine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Glaxo Wellcome
- Study completion
- Mar 1995 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis.
- Isoniazid not initiated during study period.
- Methadone maintenance.
- Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day.
Key exclusion criteria (29 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyrimethamine | Drug | – |
| Leucovorin calcium | Drug | – |
| Zidovudine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Background: PubMed 8726001Jacobson 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
B Luft study chair
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pyrimethamine, Leucovorin calcium and Zidovudine in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000973, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.