Progressive Multifocal LeukoencephalopathyNCT01730131
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
An observational study of Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 120 yearsHealthy volunteers can take part
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2012to 1 Jan 2052
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 120 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: Primary clinical for participants that have PML or at risk for PML and community sample/healthy relatives for healthy volunteers.
Who may be able to join
- Suspected or confirmed PML
- MRI compatible with PML
- Able to participate in the studies and follow-up required by the protocol
- At least 2 years old
- Able to participate in the studies and follow-up required by the protocol
- At least 2 years old
Show all 9Show fewer
- Impaired immune function from any cause and considered at risk for PML (i.e.-history of hematological malignancy, chronic inflammatory disease, history of treatment with immune suppressive or immunomodulatory therapies, primary or acquired immunodeficiency syndromes)
- Able to participate in the studies and follow-up required by the protocol
- At least 18 years old
Who cannot join
- Significant condition, which in the judgment of the principal investigator, would make participation in the diagnostic and research parts of evaluation impossible or risky
- 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)
- Pregnancy
- Inability to provide informed consent, either directly or via legally authorized representative (LAR)
- Unwillingness to consent for collection of biological samples or their cryopreservation
- Control Patients at Risk for PML
Show all 18Show fewer
- Significant condition, which in the judgment of the principal investigator, would make participation in the diagnostic and research parts of evaluation impossible or risky
- 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)
- Pregnancy
- Inability to provide informed consent, either directly or via legally authorized representative (LAR)
- Unwillingness to consent for collection of biological samples or their cryopreservation
- Healthy Volunteers
- Impaired immune function (i.e.-history of hematological malignancy, chronic inflammatory disease, history of treatment with immune suppressive or immunomodulatory therapies, primary or acquired immunodeficiency syndromes)
- Significant condition, which in the judgment of the principal investigator, would make participation in the diagnostic and research parts of evaluation impossible or risky
- 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)
- Pregnancy
- Inability to provide informed consent, either directly or via legally authorized representative (LAR)
- Unwillingness to consent for collection of biological samples or their cryopreservation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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.
Read the 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, 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:
- Clinical, imaging, and/or laboratory features pathognomonic of JCV infection and disease course that may aid in earlier diagnosis and appropriate intervention
- 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.
- Keywords
- Encephalitis, Immune Reconstitution Syndrome, Human Immunodeficiency Virus, Multiple Sclerosis, Natural History
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal, Encephalitis, Immune Reconstitution Inflammatory Syndrome, Acquired Immunodeficiency Syndrome, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 | Participants with PML |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the baseline presentation of patients with JCV infection and/or PML with regard to clinical, radiological, immunological, genetic and viral features.
- 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
Measured: one year following last enrollment
Secondary outcomes (1)
To longitudinally follow patients with JCV infection and/or PML with thorough characterization of their clinical course, imaging correlates, immunological markers, and viral studies
- 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
Measured: one year following last enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study start8 Nov 2012
- Primary completion1 Jan 2052 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Irene CM Cortese, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01730131
- Sponsor's protocol ID
- 130017
- Other IDs
- 13-N-0017
- Status last verified
- 4 Aug 2026
- First submitted
- 17 Nov 2012
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 19778765Padgett 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.
PubMed 4104715Gheuens 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.
PubMed 19828476
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
- ClinicalTrials.gov ID
- NCT01730131
- Acronym / sponsor ID
- 130017
- Keywords
- Encephalitis, Immune Reconstitution Syndrome, Human Immunodeficiency Virus, Multiple Sclerosis, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 8 Nov 2012 (actual)
- Primary completion
- 1 Jan 2052 (estimated)
- First posted
- 21 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- Clinical, imaging, and/or laboratory features pathognomonic of JCV infection and disease course that may aid in earlier diagnosis and appropriate intervention
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 | – | –Participants with PML |
Who may qualify
- Ages
- 2 to 120 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Primary clinical for participants that have PML or at risk for PML and community sample/healthy relatives for healthy volunteers.
Key inclusion criteria (9 listed)
- Suspected or confirmed PML
- MRI compatible with PML
- Able to participate in the studies and follow-up required by the protocol
- At least 2 years old
- Able to participate in the studies and follow-up required by the protocol
Key exclusion criteria (18 listed)
- Significant condition, which in the judgment of the principal investigator, would make participation in the diagnostic and research parts of evaluation impossible or risky
- 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)
- Pregnancy
- Inability to provide informed consent, either directly or via legally authorized representative (LAR)
- Unwillingness to consent for collection of biological samples or their cryopreservation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To characterize the baseline presentation of patients with JCV infection and/or PML with regard to clinical, radiological, immunological, genetic and viral features.
Time frame: one year following last enrollment
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
1 secondary outcome
To longitudinally follow patients with JCV infection and/or PML with thorough characterization of their clinical course, imaging correlates, immunological markers, and viral studies
Time frame: one year following last enrollment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Background: PubMed 19778765Cinque 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.
- Background: PubMed 4104715Padgett 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.
- Background: PubMed 19828476Gheuens 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Irene CM Cortese, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Progressive Multifocal Leukoencephalopathy, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mauricio A Campillay ((301) 496-3825, mauricio.campillay@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize the baseline presentation of patients with JCV infection and/or PML with regard to clinical, radiological, immunological, genetic and viral features. (time frame: one year following last enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01730131, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.