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A Phase I/II Pilot Treatment Study Of CSF Penetration And Response To Ganciclovir And Foscarnet In CMV Neurologic Disease.

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What is being tested

Foscarnet sodium

+ Ganciclovir
Drug
Who is being recruted

Encephalopathy

+ HIV Infections
+ Radiculitis
Over 13 Years
How is the trial designed

Treatment Study

Phase 1
Interventional

Summary

Principal SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last updated: October 29, 2021
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To determine the safety and CSF penetration of combined ganciclovir and foscarnet treatment for presumed cytomegalovirus encephalitis or radiculomyelopathy. This study proposes to investigate the use of combined ganciclovir and foscarnet to maximize the antiviral regimen. Current evidence suggests that a combination of ganciclovir and foscarnet may be the most efficacious therapy and appears to be well tolerated. This study will provide key information regarding safety and CSF penetration of the drugs available for treatment of these lethal diseases. It will also provide preliminary information regarding virologic factors relevant to CMV CNS disease. The study will also provide further data about the natural history of CMV brain infection detected by a combination of symptom complex and PCR identification of CMV in CSF and the potential of semi-quantitative PCR evaluation of the CSF for the disease. This study proposes to investigate the use of combined ganciclovir and foscarnet to maximize the antiviral regimen. Current evidence suggests that a combination of ganciclovir and foscarnet may be the most efficacious therapy and appears to be well tolerated. This study will provide key information regarding safety and CSF penetration of the drugs available for treatment of these lethal diseases. It will also provide preliminary information regarding virologic factors relevant to CMV CNS disease. The study will also provide further data about the natural history of CMV brain infection detected by a combination of symptom complex and PCR identification of CMV in CSF and the potential of semi-quantitative PCR evaluation of the CSF for the disease. Patients will be stratified by clinical syndrome as having either primarily A) encephalitis; or B) radiculomyelitis. If patient has combined encephalitis and radiculomyelitis, then the patient will be stratified as encephalitis. CMV therapy with ganciclovir and foscarnet will first be given at an induction level and then a maintenance level. For the first 4 weeks, patients will be given foscarnet plus ganciclovir. Then for the following 20 weeks, patients will be given foscarnet plus ganciclovir with ganciclovir at a lower dose. NOTE: A maximum of 10 patients that have proven to be intolerant to either foscarnet or ganciclovir may receive the alternate agent alone. NOTE: Ganciclovir experienced subjects will be given GCV at induction and maintenance doses if tolerated. NOTE: Induction doses will not be re-started in the face of clinical relapse on switching to maintenance therapy.

Official TitleA Phase I/II Pilot Treatment Study Of CSF Penetration And Response To Ganciclovir And Foscarnet In CMV Neurologic Disease. 
Principal SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last updated: October 29, 2021
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 13 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Encephalopathy
HIV Infections
Radiculitis
Criteria

Inclusion Criteria Concurrent Medication: Allowed: Patients with treated, stable toxoplasmosis encephalitis with documented stable CT or MR scans may be enrolled if maintenance suppressive therapy is continued. Patients must have: * Documented HIV infection. * Encephalopathy or radiculomyelitis. * CSF positive for CMV by PCR. * Signed informed consent from a parent or legal guardian for patients \< 18 years. * CSF cytological analysis should be obtained at the time of enrollment or within 2 weeks prior to enrollment. NOTE: * Co-enrollment is encouraged where study procedures do not conflict. Protocols investigating antiviral regimens with potential activity against CMV or other human herpes viruses will be ineligible. Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: * Active CNS infection or malignancy, other than due to CMV or HIV. * A positive CSF VDRL. * Any evidence of active disease such as a substantial increase in cryptococcal antigen titer or positive culture. However, patients may be enrolled with stable, treated cryptococcal meningitis. * A dermatomal or disseminated varicella-zoster infection within 30 days prior to enrollment. * An active, symptomatic systemic infection, other tan HIV or CMV, for which the patient is not receiving stable therapy for at least 30 days. * Any other advanced disease likely to cause death in \<6 months. * Known intolerance to both foscarnet and ganciclovir. * Inability to safely perform a lumbar puncture. Concurrent Medication: Excluded: * Patients on prophylactic antiviral therapy at the time of study enrollment will not be allowed to continue this medication during the study. In the event of the appearance of HSV or VZV infections after enrollment in the study that require systemic therapy, acyclovir or other appropriate medication may be instituted. * Patients may not receive ZDV therapy during the initial 4 weeks of the study. Concurrent ZDV therapy will be started during maintenance therapy if tolerated. Bone marrow sparing antiretroviral therapy may be used at the investigator's discretion. NOTE: * Concurrent medications should be kept to a minimum because of possible interference with the assessment of both safety and pharmacokinetics. But medications absolutely necessary for the subject's welfare may be administered at the discretion of the investigator.



Study Centers

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