Observational Study on Characteristics and Survival Correlates of Progressive Multifocal Leukoencephalopathy (PML) in Italy

NCT06594614 | Completed

• 1 other identifier: Milano PML cohort
• Study Type: observational
• Target: 456
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn about the features of Progressive Multifocal Leukoencephalopathy (PML) at the time of its diagnosis and the factors that may influence the outcome of persons with this disease. PML is a rare and rapidly progressive disease of the brain, caused by a virus named JC polyomavirus (JCV). This disease almost always occurs in persons with an immune dysfunction. In some people, the underlying immune dysfunction may be the consequence of other conditions, such as certain hematological tumors (for instance, some lymphomas) or the infection with the Human Immune Deficiency Virus (HIV). In other cases it may be associated with other forms of immune deficiency, either present at birth or acquired later in life, or with immunosuppressive or immunomodulant treatments, such as Natalizumab in persons with Multiple Sclerosis. Unfortunately, there is no cure for PML, and the only possibility to stop the progression of the disease is to eliminate the cause of the underlying immune dysfunction. This is not always possible, or it may take time, and, therefore, more than half of the persons who developed PML will not survive to the disease. This study takes advantage of the systematic collection, over a time frame of 37 years, of the characteristics of 456 cases of PML. The main question of this study aims to answer whether and how PML characteristics and outcome have evolved over time and also according to the disease or condition that caused the immune dysfunction leading to PML. This is important because PML is a rare disease, and, therefore, knowing the context in which it develops can be useful for healthcare providers and families to consider PML as a possible cause of unexpected neurological problems. In fact, an early recognition of PML is associated with a better outcome. On the other hand, there are clinical and laboratory features of PML that can also be associated with different disease outcome. Therefore, it is important that these features are identified, to provide important information for disease management and also for the design of experimental therapeutic interventions. Participants of this study are persons with a diagnosis of PML who were followed at the Infectious Diseases Unit of San Raffaele Hospital in Milan or referred to the Unit from other Italian clinical centers, between January 1st 1987 and April 30th 2024. We have retrospectively reviewed their clinical charts and collected demographic characteristics, together with the clinical, radiological and laboratory features of PML at the time of its diagnosis. In addition we have also reviewed the evolution of the disease one-year after the date of diagnosis. The data from the participants have been collected in a custom-made database, which is kept updated with follow-up data and inclusion of new participants. As by April 30th 2024, 456 participants have been included in the database. This is one of the largest existing cohorts and the one with the longest observational window. In addition, and differently from previous cohort studies, it analyzes in detail clinical, radiological, and virological characteristics of PML, providing additional information on their changes over time and possible predictors of disease outcome.

Conditions

Progressive Multifocal Leukoencephalopathy; PML

Keywords

Progressive Multifocal Leukoencephalopathy; PML; epidemiology; survival; JCV-DNA; cerebrospinal fluid; JCV; JC virus; JC human polyomavirus; Human polyomavirus 2

Outcome Measures

Primary Outcomes (1)

• To evaluate the characteristics of PML patients over time and according to the underlying PML condition

  To evaluate the characteristics of PML patients (demographics, clinical, laboratory) over time and according to the underlying PML condition

  At the time of PML diagnosis

Secondary Outcomes (1)

• To assess PML patients' survival and associated variables

  One year

Study Arms (1)

Patients with Progressive Multifocal Leukoencephalopathy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with a diagnosis of PML, achieved by either JCV-DNA identification in the cerebrospinal fluid (CSF) or biopsy/autopsy, or a possible diagnosis based on clinico-radiological data, following revision of magnetic resonance imaging (MRI) exams by a PML expert neuroradiologist

You may qualify if:

• Definitive PML diagnosis by either JCV-DNA identification in the cerebrospinal fluid (CSF) or biopsy/autopsy, or a possible diagnosis based on clinico-radiological data, following revision of magnetic resonance imaging (MRI) exams by a PML expert neuroradiologist
• Known year of PML diagnosis
• Known underlying condition predisposing to PML development

Sponsors & Collaborators

• Scientific Institute San Raffaele: lead

Study Sites (1)

San Raffaele Scientific Institute

Milan, MI, 20127, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid, plasma, PBMCs

MeSH Terms

Conditions

Leukoencephalopathy, Progressive Multifocal

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

Study Officials

• Paola Cinque, MD, PhD

  San Raffaele Scientific institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinical Research Unit

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: January 1, 1987
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)