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A Phase I/II Pilot Treatment Study Of CSF Penetration And Response To Ganciclovir And Foscarnet In CMV Neurologic Disease.
This study has been terminated.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000856
  Purpose

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.


Condition Intervention Phase
Encephalopathy
HIV Infections
Radiculitis
Drug: Foscarnet sodium
Drug: Ganciclovir
Phase I

MedlinePlus related topics: AIDS Cytomegalovirus Infections Encephalitis
Drug Information available for: Ganciclovir Ganciclovir sodium Foscarnet Foscarnet sodium Fosfonet sodium Phosphonoacetic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Parallel Assignment, Safety Study
Official Title: A Phase I/II Pilot Treatment Study Of CSF Penetration And Response To Ganciclovir And Foscarnet In CMV Neurologic Disease.

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

Estimated Enrollment: 30
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000856

Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, New York
Mount Sinai Med Ctr
New York, New York, United States, 10029
United States, Ohio
MetroHealth Med Ctr
Cleveland, Ohio, United States, 441091998
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: Clifford D
Study Chair: Tselis A
  More Information

Click here for more information about Ganciclovir  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: ACTG 305
Study First Received: November 2, 1999
Last Updated: July 31, 2008
ClinicalTrials.gov Identifier: NCT00000856  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Ganciclovir
Drug Therapy, Combination
Encephalitis
Foscarnet
Cytomegalovirus Infections
Antiviral Agents
Radiculopathy

Study placed in the following topic categories:
Opportunistic Infections
Phosphonoacetic Acid
Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Ganciclovir
Cytomegalovirus
Encephalitis
Immunologic Deficiency Syndromes
Virus Diseases
Neuromuscular Diseases
HIV Infections
Peripheral Nervous System Diseases
AIDS-Related Opportunistic Infections
Radiculopathy
Sexually Transmitted Diseases
Cytomegalovirus Infections
Foscarnet
Cytomegalic inclusion disease
Retroviridae Infections

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Nervous System Diseases
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009