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

NCT00000856 | Withdrawn Phase 1

• 2 other identifiers: ACTG 30511280
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Encephalopathy; HIV Infections; Radiculitis

Keywords

AIDS-Related Opportunistic Infections; Ganciclovir; Drug Therapy, Combination; Encephalitis; Foscarnet; Cytomegalovirus Infections; Antiviral Agents; Radiculopathy

Interventions

Foscarnet sodium DRUG

Ganciclovir DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

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

Related Publications (1)

• Smart T. Responding to CMV neurologic infections. GMHC Treat Issues. 1996 Nov;10(11):5-7, 10.

  PMID: 11364010 BACKGROUND

MeSH Terms

Conditions

Brain Diseases; HIV Infections; Radiculopathy; AIDS-Related Opportunistic Infections; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Encephalitis; Cytomegalovirus Infections

Interventions

Foscarnet; Ganciclovir

Condition Hierarchy (Ancestors)

Central Nervous System Diseases; Nervous System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; 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; Peripheral Nervous System Diseases; Neuromuscular Diseases; Opportunistic Infections; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases; Neuroinflammatory Diseases; Herpesviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Phosphonoacetic Acid; Acetates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Organophosphonates; Organophosphorus Compounds; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clifford D

  STUDY CHAIR

• Tselis A

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Last Updated: October 29, 2021

Record last verified: 2021-10