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Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)

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ClinicalTrials.gov Identifier: NCT01730131
Recruitment Status : Recruiting
First Posted : November 21, 2012
Last Update Posted : May 11, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

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.

Condition or disease
Progressive Multifocal Leukoencephalopathy

Detailed Description:

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 and cerebrospinal fluid (CSF) 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.

Specifically, this detailed characterization 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 intervention
  2. Clinical imaging and/or laboratory features of the disease course that is 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; this data and biological bank will be made available to outside laboratories.

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Actual Study Start Date : November 8, 2012
Estimated Primary Completion Date : December 1, 2023
Estimated Study Completion Date : May 1, 2025

Resource links provided by the National Library of Medicine


Group/Cohort
Control Patients at Risk for PML
Participants with impaired immune function from any cause and considered at risk for PML
Healthy Volunteers
Healthy volunteers without impaired immune function
PML Patients
Patients with PML



Primary Outcome Measures :
  1. To characterization the baseline features, of patients with PML with regards to clinical features imaging studies, immunological markers, and viral studies. [ Time Frame: one year following last enrollment ]
    1. Characterization of distinctive imaging features to differentiate between actively progressing PML, and PML-IRIS and inactive PML2. Characterization of distinctive clinical features to differentiate between actively progressing PML, PML- and IRIS, and inactive PML3. Characterization of immune and virological features to differentiate between actively progressing PML, and PML- IRIS, 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 individuals 5. Characterization of genetic susceptibility for development of PML


Secondary Outcome Measures :
  1. To longitudinally follow patients with PML with thorough characterization of their clinical course, imaging correlates, immunological markers, and viral studies [ Time Frame: one year following last enrollment ]
    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 studies



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Primary clinical for participants that have PML or at risk for PML and community sample/healthy relatives for healthy volunteers.
Criteria
  • 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 appointed power of attorney
  5. Unwillingness to consent for collection of biological samples or their cryopreservation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01730131


Contacts
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Contact: Amanda M Wiebold (301) 594-5194 amanda.wiebold@nih.gov
Contact: Irene CM Cortese, M.D. (301) 496-9175 corteseir@ninds.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Irene CM Cortese, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
Publications:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT01730131    
Other Study ID Numbers: 130017
13-N-0017
First Posted: November 21, 2012    Key Record Dates
Last Update Posted: May 11, 2020
Last Verified: April 24, 2020
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Encephalitis
Immune Reconstitution Syndrome
Human Immunodeficiency Virus
Multiple Sclerosis
Additional relevant MeSH terms:
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Leukoencephalopathy, Progressive Multifocal
Leukoencephalopathies
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Viral
Central Nervous System Viral Diseases
Virus Diseases
Polyomavirus Infections
DNA Virus Infections
Slow Virus Diseases
Infectious Encephalitis
Encephalitis
Central Nervous System Infections
Demyelinating Diseases