Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)

NCT ID: NCT01730131

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

700 participants

Study Classification

OBSERVATIONAL

Study Start Date

2012-11-08

Brief Summary

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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:

* Participants will be screened with a physical exam, medical history, and imaging studies.
* Participants will have several visits to the National Institutes of Health Clinical Center. There will be an initial visit, monthly visits for the next 6 months, a 12-month visit, and possible visits afterward.
* At the initial visit, participants will give blood, urine, and spinal fluid samples. They will also have neurological tests and imaging studies of the brain.
* For the next five visits, participants will give blood and urine samples. They will also have neurological tests and imaging studies of the brain.
* The 6-month and 12-month visits will repeat the tests from the initial visit.
* Other optional procedures include bone marrow samples and skin biopsies. Additional blood tests and imaging studies may be performed.
* Treatment will not be provided as part of this study.

Detailed Description

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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:

1. Clinical, imaging, and/or laboratory features pathognomonic of JCV infection and disease course that may aid in earlier diagnosis and appropriate intervention
2. Clinical, imaging, and/or laboratory features of JCV infection and disease course that are predictive of clinical outcomes

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.

Conditions

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Progressive Multifocal Leukoencephalopathy

Keywords

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Encephalitis Immune Reconstitution Syndrome Human Immunodeficiency Virus Multiple Sclerosis Natural History

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Control Patients at Risk for PML

Participants with impaired immune function from any cause and considered at risk for PML

No interventions assigned to this group

Healthy Volunteers

Healthy volunteers without impaired immune function

No interventions assigned to this group

PML Patients

Participants with PML

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Suspected or confirmed PML
2. MRI compatible with PML
3. Able to participate in the studies and follow-up required by the protocol
4. At least 2 years old

Exclusion Criteria

1. Significant condition, which in the judgment of the principal investigator, would make participation in the diagnostic and research parts of evaluation impossible or risky
2. Medical contraindication to MRI (i.e., devices such as a cardiac pacemaker or infusion pump, other metallic implants, metallic foreign objects, body piercings that cannot be removed)
3. Pregnancy
4. Inability to provide informed consent, either directly or via legally authorized representative (LAR)
5. Unwillingness to consent for collection of biological samples or their cryopreservation
Minimum Eligible Age

2 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Irene CM Cortese, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Neurological Disorders and Stroke (NINDS)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mauricio A Campillay

Role: CONTACT

Phone: (301) 496-3825

Email: [email protected]

Irene CM Cortese, M.D.

Role: CONTACT

Phone: (301) 496-1801

Email: [email protected]

Facility Contacts

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For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

References

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Cinque P, Koralnik IJ, Gerevini S, Miro JM, Price RW. Progressive multifocal leukoencephalopathy in HIV-1 infection. Lancet Infect Dis. 2009 Oct;9(10):625-36. doi: 10.1016/S1473-3099(09)70226-9.

Reference Type BACKGROUND
PMID: 19778765 (View on PubMed)

Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971 Jun 19;1(7712):1257-60. doi: 10.1016/s0140-6736(71)91777-6. No abstract available.

Reference Type BACKGROUND
PMID: 4104715 (View on PubMed)

Gheuens S, Pierone G, Peeters P, Koralnik IJ. Progressive multifocal leukoencephalopathy in individuals with minimal or occult immunosuppression. J Neurol Neurosurg Psychiatry. 2010 Mar;81(3):247-54. doi: 10.1136/jnnp.2009.187666. Epub 2009 Oct 14.

Reference Type BACKGROUND
PMID: 19828476 (View on PubMed)

Related Links

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Other Identifiers

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13-N-0017

Identifier Type: -

Identifier Source: secondary_id

130017

Identifier Type: -

Identifier Source: org_study_id