Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier:
NCT01730131
First received: November 17, 2012
Last updated: June 11, 2014
Last verified: May 2014
  Purpose

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
Progressive Multifocal Leukoencephalopathy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Characterization of the baseline features of patients with PMLwith regards to clinical features imaging studies,immunological markers, and viral studies. [ Time Frame: every 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: November 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Detailed Description:

The objective of this study is to examine the natural course of 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 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.

Specifically, this detailed characterization will be used to help identify:

  1. Clinical and/or imaging features pathognomonic of PML 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. CSF or brain biopsy positive for JCV
    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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01730131

Contacts
Contact: Avindra Nath, M.D. (301) 496-1561 natha@mail.nih.gov

Locations
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 Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Avindra Nath, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )
ClinicalTrials.gov Identifier: NCT01730131     History of Changes
Other Study ID Numbers: 130017, 13-N-0017
Study First Received: November 17, 2012
Last Updated: June 11, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immune Reconstitution Syndrome
Human Immunodeficiency Virus
Multiple Sclerosis

Additional relevant MeSH terms:
Leukoencephalopathies
Leukoencephalopathy, Progressive Multifocal
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Virus Diseases
Polyomavirus Infections
DNA Virus Infections
Slow Virus Diseases
Central Nervous System Infections
Demyelinating Diseases

ClinicalTrials.gov processed this record on September 15, 2014