Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy

NCT04453917 | Completed

• 1 other identifier: RC31/19/0506
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

Progressive multifocal leukoencephalopathy (PML) is a rare viral infection of the central nervous system (CNS) occurring in immunocompromised patients. Recovery of JC virus (JCV) specific T cell immune responses is the only available therapeutic option. JCV may use immune checkpoint inhibitory pathways to evade immune responses. The aim of this project is to determine whether T cell expression of immune checkpoint molecules is correlated to antiviral T cell responses, control of JCV replication and PML outcome. Immune checkpoint blockade by reversing T cell exhaustion may represent a therapeutic perspective for PML.

Conditions

Progressive Multifocal Leukoencephalopathy

Keywords

Progressive multifocal leukoencephalopathy; Pathophysiology; Immune checkpoint molecules; Immune Checkpoint Inhibitors

Outcome Measures

Primary Outcomes (9)

• Immune checkpoint molecules

  Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry

  1 month

• Immune checkpoint molecules

  Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry

  3 months

• Immune checkpoint molecules

  Expression level of a broad panel of immune checkpoint molecules by T cells at PML diagnosis bu flow cytometry

  6 months

• JC viral load

  JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis

  1 month

• JC viral load

  JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis

  3 months

• JC viral load

  JC viral load in cerebrospinal fluid, blood and urine by ultra-sensitive PCR at PML diagnosis

  6 months

• Detection of immune responses against a JCV peptide library

  Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry

  1 month

• Detection of immune responses against a JCV peptide library

  Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry

  3 months

• Detection of immune responses against a JCV peptide library

  Detection of specific immune responses against a JCV peptide library at PML diagnosis by flow cytometry

  6 months

Secondary Outcomes (6)

• Differential impact of immune checkpoint inhibition

  1 month, 3 months and 6 months

• Clinical outcome with Performance status

  1 month, 3 months and 6 months

• Clinical outcome with NIHSS

  1 month, 3 months and 6 months

• Clinical outcome with Rankin

  1 month, 3 months and 6 months

• Neuroradiological monitoring

  3 months and 6 months

Study Arms (1)

Patients with active PML

EXPERIMENTAL

Patients with neurological symptoms (\< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV

Biological: Collection of blood and urine; Biological: Spinal tap; Diagnostic Test: Brain MRI; Biological: Neurological evaluation

Interventions

Brain MRI DIAGNOSTIC_TEST

Brain MRI at at PML diagnosis and 3 and 6 months after

Patients with active PML

Neurological evaluation BIOLOGICAL

Neurological evaluation at PML diagnosis and 1, 3 and 6 months after

Patients with active PML

Collection of blood and urine BIOLOGICAL

Collection of blood (47 mL) and urine (5 mL) at PML diagnosis and 1, 3 and 6 months after, for analysis of immune checkpoint molecules expression, detection of antiviral immune responses and virological analyses.

Patients with active PML

Spinal tap BIOLOGICAL

Spinal tap for monitoring of JC viral load at PML diagnosis and 1, 3 and 6 months after, and collection of CSF (2 mL) for virological analyses.

Patients with active PML

Eligibility Criteria

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

You may qualify if:

• Adults ≥18 years old
• Informed consent
• Active virological PML : Recent neurological symptoms (\< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV
• Affiliated or benefiting from public health insurance.

You may not qualify if:

• Non active PML
• Possible PML with negative JCV PCR
• Adults under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
• Pregnant and/or breastfeeding women

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (3)

CHU Bordeaux

Bordeaux, France

Location

CHU Montpellier

Montpellier, France

Location

CHU de TOULOUSE

Toulouse, 31000, France

Location

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal

Interventions

Urination; Spinal Puncture

Condition Hierarchy (Ancestors)

Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Virus Diseases; Polyomavirus Infections; DNA Virus Infections; Slow Virus Diseases; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies; Demyelinating Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Guillaume MARTIN-BLONDEL

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with neurological symptoms (\< 3 months) with brain MRI lesions suggestive of PML and positive PCR in cerebrospinal fluid for JCV

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: July 1, 2020
• Study Start: February 23, 2021
• Primary Completion: July 12, 2024
• Study Completion: July 12, 2024
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)