View Clinical Trial (Medical Research Study)
PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [(11)C]PBR28 in Patients With Multiple Sclerosis (MS)
| City: |
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Bethesda |
| State: |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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Multiple Sclerosis |
| Purpose: |
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This study will use positron emission tomography (PET) to measure a brain protein called
peripheral benzodiazepine receptor (PBR) in patients with multiple sclerosis. PBR is created
during the inflammation process, and brain inflammation is a key feature of multiple
sclerosis (MS). PBR usually affects one type of brain cell, but it can also cause damage to
surrounding areas of the brain in patients with MS. PET studies of PBRs and brain
inflammation may help elucidate the role of these brain cells in patients with MS.
Healthy normal volunteers and patients with MS between 18 and 70 years of age may be
eligible for this study. Patients with MS must have had onset of disease between 18 and 40
years of age.
Patients with MS undergo the following procedures:
Visit 1: Medical history, physical examination, blood tests and magnetic resonance imaging
(MRI).
Visit 2: Blood tests and PET scan.
Visits 3 and 4: MRI and physical examination.
Visit 5: PET scan and blood tests.
Visit 6: MRI and physical examination.
Healthy volunteers undergo the following:
Visit 1: Medical history, physical examination, blood tests.
Visits 2 and 3: PET and blood tests.
Magnetic Resonance Imaging
MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For
this procedure, the subject lies on a table that can slide in and out of the scanner (a
metal cylinder), wearing earplugs to muffle loud knocking noises that occur during the
scanning process. The procedure lasts about 90 minutes; the patient is asked to lie still
for up to 25 minutes at a time. The subject can communicate with the MRI staff at all times
during the scan. During part of the scan a contrast agent is administered through a catheter
(plastic tube) placed in an arm vein to enhance the images.
Positron Emission Tomography (PET)
The PET scan gives information on brain and body chemistry and function. The subject lies on
a bed that slides in and out of the doughnut-shaped scanner. A catheter is placed in a vein
in the arm and another is placed in an artery in the wrist or elbow area. The catheter in
the arm is used for injecting a radioactive material that the scanner detects, and the other
is used to collect blood samples. A custom-molded plastic mask is used to support the head
and prevent it from moving during the procedure. The subject may be asked to perform various
tasks during the PET scan or to lie quietly. The scan lasts about 2.5 hours.
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| Study Summary: |
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OBJECTIVE:
The primary objective of this study is to measure brain peripheral benzodiazepine receptor
(PBR) expression as a marker of neuroinflammation in subjects with MS using [(11)C]PBR28 PET
imaging. Inflammation in the central nervous system (CNS) is a prominent feature of
multiple sclerosis (MS), the leading cause of neurological disability in young adults. A
complex sequence of inflammatory events leads to the formation of new lesions. The
disruption of blood-brain barrier that occurs during this inflammatory cascade is the basis
of Gadolinium-DTPA (Gd-DTPA) enhancing lesion on magnetic resonance imaging (MRI), currently
the most widely utilized marker of neuroinflammation in MS. Although Gd-DTPA enhancement
correlates with acute clinical relapses, its limitation as a biomarker of disease activity
includes the relative insensitivity to mild degrees of inflammation and the lack of
correlation to long-term disability. An alternative marker of neuroinflammation may,
therefore, be informative. Activated microglia and macrophage constitute the secondary
effector cells of CNS inflammation in MS. Recent studies investigating the expression of
the peripheral benzodiazepine receptor (PBR) in the CNS have shown that the increased
expression of PBR is a marker of activated microglia/macrophage. Specific ligands for PBR
have allowed the study of activated microglia/macrophage in vivo through positron emission
tomography (PET) imaging in a number of settings including inflammatory, ischemic and toxic
injury to the CNS. The availability of a novel PBR ligand [(11)C]PBR28 developed by the
Molecular Imaging Branch, NIMH, that demonstrated greater specific signal for PBR than the
previously available ligands affords a unique opportunity to investigate a cell-type
specific marker of neuroinflammation in MS.
STUDY POPULATION:
Subjects with definite MS (McDonald criteria) with evidence of brain inflammatory activity
indicated by presence of Gd-DTPA enhancing lesions on MRI and a control group consisting of
age-matched healthy volunteers.
DESIGN:
Up to 32 subjects with MS will undergo screening whole body [(11)C]PBR28 PET scan to accrue
up to 16 MS subjects with confirmed [(11)C]PBR28 PET binding who will undergo a brain
[(11)C]PBR28 PET and MRI imaging. Subjects with MS will undergo follow-up brain
[(11)C]PBR28 PET and MRI at approximately 4-month interval. Subjects will undergo clinical
examination at each PET imaging time point to assess clinical measures of disability and
impairment. Up to an equal number of age-matched healthy volunteers will undergo screening
whole body [(11)C]PBR28 PETscan. Up to 16 healthy volunteers with confirmed [(11)C]PBR28 PET
binding on the screening will undergo test retest brain [(11)C]PBR28 PET studies to
determine the reproducibility of [(11)C]PBR28 PET in a healthy population compared to MS.
OUTCOME MEASURES:
The study seeks to test PBR expression measured by [(11)C]PBR28 PET imaging as a marker of
neuroinflammation in patients with MS. Primary outcome measures include 1) correlation
between increased PBR expression and gadolinium-enhancing lesions on MRI, and 2) correlation
between increased PBR expression and previously and/or persistently gadolinium-enhancing
lesions on MRI, 3) PBR expression in subjects with multiple sclerosis compared to that in
healthy volunteers.
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| Criteria: |
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- SUBJECTS WITH MULTIPLE SCLEROSIS - INCLUSION CRITERIA:
- Ages between 18 and 70, inclusive.
- Diagnosis of definite MS according to published criteria.
- The presence of at least one gadolinium-enhancing lesion on the screening brain
magnetic resonance image (MRI), and T2 lesion load volume greater than 5 cc.
- Subjects must be able to provide written, informed consent prior to any testing under
this protocol, including screening and baseline investigations that are not
considered part of routine patient care.
SUBJECTS WITH MULTIPLE SCLEROSIS - EXCLUSION CRITERIA:
- Prior participation in other research protocols or clinical care in the last year
such that radiation exposure would exceed the annual guidelines.
- "Non-binding" on screening whole body [ (11)C]PBR28 PET Scan
- Pregnancy and breast-feeding.
- Presence of ferromagnetic metal in the body or heart pacemaker.
- ECG with clinically significant abnormalities.
- Positive HIV test.
- Positive pregnancy test.
- Concurrent medical conditions including hepatic cirrhosis, end-stage renal disease or
any acute and severe decompensation of disease that in the opinion of the
investigator would compromise the safety of the patient.
- Subjects with cognitive impairment who are unable to provide written, informed
consent.
- Subjects who have received immunomodulatory/disease-modifying therapy, including
investigational MS therapy, within 12 weeks prior to PET imaging or who have received
corticosteroids within 6 weeks prior to PET imaging.
HEALTHY VOLUNTEERS - INCLUSION CRITERIA:
All subjects must be healthy and aged 18-70 years.
HEALTHY VOLUNTEERS - EXCLUSION CRITERIA:
'Non-binding' on screening whole body [(11)C]PBR28 PET scan.
Current psychiatric illness, substance abuse or severe systemic disease based on history
and physical exam.
ECG with clinically significant abnormalities. Any existing physical exam and ECG within
one year will be reviewed and if none already exists in the chart, these will be obtained
and reviewed.
Laboratory tests with clinically significant abnormalities.
Prior participation in other research protocols in the last year such that radiation
exposure would exceed the annual guidelines.
Pregnancy and breast-feeding.
Positive pregnancy test.
Claustrophobia.
Presence of ferromagnetic metal in the body or heart pacemaker.
Positive HIV test.
A history of brain disease.
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| NCT ID: |
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NCT00432900 |
| Primary Contact: |
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Principal Investigator
Steven Jacobson, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Joan M Ohayon, C.R.N.P.
Phone: (301) 496-0064
Email: ohayonj@ninds.nih.gov
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| Backup Contact: |
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Email: jacobsons@mail.nih.gov
Steven Jacobson, Ph.D.
Phone: (301) 496-0519
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| Location Contact: |
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Bethesda, Maryland 20892
United States
For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)
Phone: 800-411-1222
Email: prpl@mail.cc.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 22, 2013 |
| Modifications to this listing: |
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