Ignite Creation Date:
2024-05-05 @ 5:21 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00432900
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
2007-02-07
Brief Title:
Brain Peripheral Benzodiazepine Receptors in Patients With Multiple Sclerosis
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using 11CPBR28 in Patients With Multiple Sclerosis MS
Status:
COMPLETED
Status Verified Date:
2014-04-22
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 25 hours
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 25 hours
Detailed Description:
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 11CPBR28 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 microgliamacrophage Specific ligands for PBR have allowed the study of activated microgliamacrophage 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 11CPBR28 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 TSPO genotype analysis by PCR to accrue up to 16 MS subjects with confirmed high- or mixed- affinity binding genotype HL or HH genotype who will undergo a brain 11CPBR28 PET and MRI imaging Subjects with MS will undergo follow-up brain 11CPBR28 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 TSPO genotype analysis by PCR Up to 16 healthy volunteers with confirmed high- or mixed- affinity binding genotype HL or HH genotypeundergo test retest brain 11CPBR28 PET studies to determine the reproducibility of 11CPBR28 PET in a healthy population compared to MS
OUTCOME MEASURES
The study seeks to test PBR expression measured by 11CPBR28 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 andor persistently gadolinium-enhancing lesions on MRI 3 PBR expression in subjects with multiple sclerosis compared to that in healthy volunteers
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 11CPBR28 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 microgliamacrophage Specific ligands for PBR have allowed the study of activated microgliamacrophage 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 11CPBR28 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 TSPO genotype analysis by PCR to accrue up to 16 MS subjects with confirmed high- or mixed- affinity binding genotype HL or HH genotype who will undergo a brain 11CPBR28 PET and MRI imaging Subjects with MS will undergo follow-up brain 11CPBR28 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 TSPO genotype analysis by PCR Up to 16 healthy volunteers with confirmed high- or mixed- affinity binding genotype HL or HH genotypeundergo test retest brain 11CPBR28 PET studies to determine the reproducibility of 11CPBR28 PET in a healthy population compared to MS
OUTCOME MEASURES
The study seeks to test PBR expression measured by 11CPBR28 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 andor persistently gadolinium-enhancing lesions on MRI 3 PBR expression in subjects with multiple sclerosis compared to that in healthy volunteers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 07-N-0092 | None | None | None |