An observational study in Progressive Multifocal Leukoencephalopathy, sponsored by National Institute of Neurological Disorders and Stroke (NINDS). Recruiting at 1 site in United States. Open to participants aged 2 Years to 120 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-10-29.
Sponsored by National Institute of Neurological Disorders and Stroke (NINDS) · Observational
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain. It is caused by JC virus. Many people have this virus in their bodies all their life, but it is usually kept in check by their immune system. If the immune system does not work right because of a disease or medication, the virus becomes active and can damage cells in the brain. Not much is known about PML or how it affects the immune system. Researchers want to study people with PML to better understand the natural history of the disease.
Objectives:
- To study the natural history of PML.
Eligibility:
- Individuals at least 2 years of age who have PML.
Design:
The objective of this study is to examine the risk factors and natural course of JCV infection and progressive multifocal leukoencephalopathy (PML). PML is a devastating, demyelinating neurological disease affecting the brain of patients with a compromised immune system. It is caused by reactivation of JC virus (JCV), a small DNA virus that infects the majority of the population without clinical significance. There are currently no treatments available for PML.
We plan to study patients with suspected or confirmed PML with different underlying conditions including patients on immune-modulatory therapies for multiple sclerosis (MS), rheumatologic diseases or other autoimmune diseases, as well as patients with HIV infection or other conditions leading to a compromised immune system. Patients will be seen at defined time points during their disease course and detailed assessments will be performed to collect clinical and imaging data. Blood, cerebrospinal fluid (CSF) and urine will also be collected at these time points to evaluate the behavior and biology of the JCV and the patients' immune responses to the infection. These tests will lead to a better understanding of the pathophysiology of PML and the course of this disease in different patient groups. Additionally, we will recruit a patient control cohort represented by patients with impaired immune function for any cause and considered at risk for development of PML, and a healthy volunteer cohort. The purpose of these additional cohorts is to explore and validate biomarkers for risk of development of PML and early diagnosis. Additionally, the healthy volunteer cohort may be screened and evaluated as possible donors of peripheral blood mononuclear cells (PBMC) for manufacture of virus-specific T cells.
The detailed characterization described above will be used to help identify:
This information will be integrated to develop a clinically relevant, disease-specific assessment scale of PML, which is currently not available. Such a scale would be a useful tool for the clinical management of patients (i.e., for development of standards of care), as well as for clinical trial design and interpretation.
The long-term objectives of this study are to improve the understanding of the disease course and underlying pathophysiology, to identify subgroups with different prognosis and/or susceptibility to interventions, and to help identify therapeutic targets and/or intervention strategies. Equally important, these efforts will allow development of a repository of cryopreserved biological samples that will be used for validation of candidate biomarkers in future studies.
29 studies on the registry are indexed under Leukoencephalopathy, Progressive Multifocal; 7 are open to participants now.
This study's planned enrollment of 700 is above the median of 96 across 12 observational studies indexed under Leukoencephalopathy, Progressive Multifocal.
Browse Leukoencephalopathy, Progressive Multifocal studies →National Institute of Neurological Disorders and Stroke (NINDS) is the lead sponsor of 601 studies on the registry; 56 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 8 (44%) have results posted.
Counted across the registry records on this site, refreshed daily.
Primary clinical for participants that have PML or at risk for PML and community sample/healthy relatives for healthy volunteers.
INCLUSION CRITERIA:
EXCLUSION CRITERIA:
Control Patients at Risk for PML
INCLUSION CRITERIA:
EXCLUSION CRITERIA:
Healthy Volunteers
INCLUSION CRITERIA:
EXCLUSION CRITERIA:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with impaired immune function from any cause and considered at risk for PML
Healthy volunteers without impaired immune function
Participants with PML
To characterize the baseline presentation of patients with JCV infection and/or PML with regard to clinical, radiological, immunological, genetic and viral features.
1\. Characterization of distinctive imaging features to differentiate between actively progressing PML, PML-IRIS/inflammatory PML and inactive PML2. Characterization of distinctive clinical features to differentiate between actively progressing PML, PML-IRIS/inflammatory PML, and inactive PML3. Characterization of immune and virological features to differentiate between actively progressing PML, PML-IRIS/inflammatory PML, and inactive PML4. Characterization of immune and virological differences across PML patient populations with different underlying disease, subjects at risk for developing PML, and healthy individuals5. Characterization of genetic susceptibility for development of PML
Time frame: one year following last enrollment
To longitudinally follow patients with JCV infection and/or PML with thorough characterization of their clinical course, imaging correlates, immunological markers, and viral studies
1\. Temporal correlation between clinical course and imaging and/or laboratory measures2. To identify biomarkers that can predict long-term outcome and response to treatment interventions3. To develop a clinically relevant assessment scale for PML that identifies milestones of disease progression4. To develop a repository of cryopreserved biological samples that will be used for validation of candidate biomarkers in future studies5. To characterize the immune profile in blood and CSF of patients with PML6. To determine the eligibility of PML patients for participation in other studies7. To screen and evaluate healthy subjects as donors for manufacture of virus-specific T cells (to be administered to patients under separate, dedicated protocol); to collect PBMC for the purpose of manufacture of virus-specific T cells, which will be stored in a bank and can be used for any appropriately HLA-matched recipient
Time frame: one year following last enrollment
Started Nov 2012 (actual). Primary completion is estimated for Jan 2052, 469 months after the start.
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Leukoencephalopathy, Progressive Multifocal →
National Institute of Neurological Disorders and Stroke (NINDS) →