Observational cohort of chronic brain viral infections (including PML)

Central Nervous System Chronic Viral Infections: A Cohort Study

This project will try immune checkpoint inhibitors in people with chronic central nervous system viral infections like PML to see if they lead to better long-term outcomes.

Quick facts

• Study type: Observational
• Enrollment: 66 (estimated)
• Ages: 14 Years and up
• Sex: All
• Sponsor: Peking Union Medical College Hospital (other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07512518 on ClinicalTrials.gov

What this trial studies

This ambidirectional cohort enrolls patients with chronic central nervous system viral infections—retrospectively including those with prior follow-up and prospectively for newly diagnosed cases—and observes outcomes with and without treatment by immune checkpoint inhibitors. PML diagnosis must meet either neuropathological criteria or the clinical/imaging/CSF criteria referenced to the 2013 AAN guidelines. Treatment exposure is recorded observationally rather than via randomization, and investigators will collect clinical, imaging, and CSF data to compare long-term neurological and survival outcomes. The main goal is to determine whether receipt of immune checkpoint inhibitors is associated with improved functional recovery or survival.

Who should consider this trial

Good fit: Ideal candidates are people over 14 years old with a confirmed chronic CNS viral infection—particularly PML diagnosed by neuropathology or by clinical, imaging, and CSF criteria per AAN guidelines—who can provide informed consent and attend follow-up at the site.

Not a fit: Patients without a confirmed CNS viral infection, those with primarily non-viral white matter disease, or those with contraindications to immune checkpoint inhibitors are unlikely to receive benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could improve survival and neurological recovery for patients with PML and related chronic CNS viral infections.

How similar studies have performed: Small case series and case reports have reported clinical stabilization or improvement with PD-1 pathway inhibitors in some PML patients, but no large randomized trials have yet confirmed efficacy.

Eligibility criteria

Inclusion Criteria:

1. Age \> 14 years old.
2. Confirmed diagnosis of chronic viral infection of the central nervous system (CNS).
3. Signed informed consent. The diagnosis of Progressive Multifocal Leukoencephalopathy (PML) shall meet one of the following criteria:(1) Neuropathological diagnosis: Pathological examination of brain tissue shows demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei; immunohistochemical detection of JC virus (JCV) antigen.(2) Clinical + imaging + cerebrospinal fluid (CSF) diagnosis: Clinical manifestations of progressive neurological dysfunction; neuroimaging shows single or multiple asymmetric white matter lesions with large volume, mostly involving the U-fibers, and rare mass effect; detection of JC virus DNA in cerebrospinal fluid. Specific reference shall be made to the 2013 American Academy of Neurology (AAN) diagnostic criteria.

For the diagnosis of other chronic viral infections of the central nervous system, the clinical manifestations shall be consistent with the characteristics of the relevant diseases, and the relevant viral DNA shall be detected in the cerebrospinal fluid.

The diagnosis of all cases must be independently confirmed by two physicians from the Encephalitis Professional Group, Department of Neurology, Peking Union Medical College Hospital, with consistent diagnostic results, to be included in the study. For cases with inconsistent diagnoses, the two physicians shall conduct consultations to reach a consensus. Patients with unreached diagnostic consensus shall not be included in the study.

Exclusion Criteria:

1. Presence of lumbar puncture contraindications, making it impossible to collect cerebrospinal fluid.
2. The attending physician and the researcher consider that the detection of virus in cerebrospinal fluid cannot explain the patient's clinical manifestations.
3. Inability to complete 1-year follow-up.

Where this trial is running

Beijing, Beijing Municipality

• Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Siyuan Fan

Conditions: Progressive Multifocal Leukoencephalopathy, Immune Checkpoint Inhibitors