Ignite Creation Date:
2024-05-06 @ 3:26 PM
Last Modification Date:
2024-10-26 @ 1:49 PM
Study NCT ID:
NCT04634994
Status:
UNKNOWN
Last Update Posted:
2021-07-21
First Post:
2020-11-09
Brief Title:
Novel Assessment of Synaptic Density in Progressive MS
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Novel Assessment of Synaptic Density in Progressive MS
Status:
UNKNOWN
Status Verified Date:
2021-07
Last Known Status:
RECRUITING
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:
The investigators propose to use the novel SV2a-PET ligand F-18SDM-8 to assess synaptic density in progressive MS including primary progressive multiple sclerosis PPMS and secondary progressive multiple sclerosis SPMS as compared to relapsing-remitting multiple sclerosis RRMS patients and healthy controls given its improved imaging characteristics and potential for large scale applicability
The specific aims of the study are
Aim 1 To compare the cortical and subcortical grey matter synaptic density in progressive MS patients patients with relapsing-remitting MS and healthy subjects using a novel F-18 labeled synaptic density PET ligand F-18SDM8 also known as F-18SynvesT-1
Aim 2 To compare the relationship of synaptic density PET and standard 3T MRI measures including global and regional brain atrophy and lesion load with clinical measures of physical disability cognitive impairment fatigue and depression in MS patients
Aim 3 To assess the relationship of synaptic density PET with serum neurofilament light chain NfL and with serum measurements of inflammatory markers IL-1β TNF-α IL-6 MCP-1 Monocyte Chemoattractant Protein-1 and MIF-1 Macrophage Migration Inhibitory Factor-1
The specific aims of the study are
Aim 1 To compare the cortical and subcortical grey matter synaptic density in progressive MS patients patients with relapsing-remitting MS and healthy subjects using a novel F-18 labeled synaptic density PET ligand F-18SDM8 also known as F-18SynvesT-1
Aim 2 To compare the relationship of synaptic density PET and standard 3T MRI measures including global and regional brain atrophy and lesion load with clinical measures of physical disability cognitive impairment fatigue and depression in MS patients
Aim 3 To assess the relationship of synaptic density PET with serum neurofilament light chain NfL and with serum measurements of inflammatory markers IL-1β TNF-α IL-6 MCP-1 Monocyte Chemoattractant Protein-1 and MIF-1 Macrophage Migration Inhibitory Factor-1
Detailed Description:
I Subject Selection Subjects will be recruited at the Partners MS Center 60 Fenwood Road Boston MA during routine clinical appointments by their physician or one of the other co-investigators listed on the protocol
II Study Procedures Subjects will be required to come for 3 visits for this study
Initial Visit
During the first visit subjects will be administered the screening questionnaire if that has not already been done over telephone Subjects will review and eventually sign the consent form They will be administered standardized questionnaires for cognitive testing andor other co-morbidities
PET Visit
All subjects will undergo at least one visit for PET scan During the PET scan visits all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection
PET imaging procedures
PET scanning session will be conducted at MGH Gordon Center PET scanning facility 55 Fruit Street Boston MA For PET scanning an intra-arterial catheter will be inserted into the F-18 SynVest-1 for metabolite blood sampling by a trained anesthesiologist Allens test will be performed prior to insertion of the intra-arterial catheter In the event that an arterial line cannot be established to obtain metabolite samples a venous line will be placed
In addition an intravenous IV catheter will be inserted into the radial antecubital or other arm or hand vein for injection of tracer Radiopharmaceutical will be injected as a bolus approximately 5mCi for F-18SynVest-1 followed by 5 mL of saline
The whole PET session will last up to 120 min At the time of imaging the subjects will be positioned in the gantry of a PET camera Head alignment will be made relative to the canthomeatal line using projected laser lines whose positions are known with respect to the slice positions of the scanner A head support apparatus will be used to minimize head motion Brain PET data acquisition will begin at the moment of radiotracer injection Images will be acquired using a high-resolution PETCT scanner
MRI Visit
All subjects will undergo a 3T Brain MRI during an MRI visit that may precede or follow the PET scan visit
Pregnancy screening prior to MRI
All women will be queried about their pregnancy status use of contraception and last menstrual period If they are reliably using contraception can state the timing of their last menstrual period and do not believe they could be pregnant the investigators will proceed with the MRI scan without pregnancy testing If they cannot do this then they will undergo a urine pregnancy test If a woman is seeking pregnancy and not using contraception she will undergo a urine pregnancy test
MRI imaging procedures MRI scanning session will be performed at BWH MRI facility at 60 Fenwood Road Boston MA
Several pulse sequences will be performed to image the brain There will be no intravenous contrast used for any of the MRIs
The MRI scan session will take approximately 1 hour
Imaging Data
The following data will be collected on all subjects during scanning sessions
During PET scanning brain images will be acquired in 3-D mode and dynamic acquisition scans will continue for up to 120 minutes A non-diagnostic CT scan will be performed for attenuation correction of PET transmission data at the time of initiation of scanning Blood samples will be collected via an arterial line for radiotracer analysis via the cannula other than the one used for radiotracer injection
Non Imaging Data
MS subjects Expanded Disability Severity Scale EDSS Timed 25-feet walk T25W Modified Fatigue impact Scale Hamilton Depression Rating Scale Wechsler Logical Memory paragraph recall
Healthy Controls Folstein Mini Mental Status Examination Hamilton Depression Rating Scale Wechsler Logical Memory paragraph recall
II Study Procedures Subjects will be required to come for 3 visits for this study
Initial Visit
During the first visit subjects will be administered the screening questionnaire if that has not already been done over telephone Subjects will review and eventually sign the consent form They will be administered standardized questionnaires for cognitive testing andor other co-morbidities
PET Visit
All subjects will undergo at least one visit for PET scan During the PET scan visits all women subjects of child bearing age will undergo a stat quantitative serum hCG pregnancy test and only women with a negative test will undergo the radiopharmaceutical injection
PET imaging procedures
PET scanning session will be conducted at MGH Gordon Center PET scanning facility 55 Fruit Street Boston MA For PET scanning an intra-arterial catheter will be inserted into the F-18 SynVest-1 for metabolite blood sampling by a trained anesthesiologist Allens test will be performed prior to insertion of the intra-arterial catheter In the event that an arterial line cannot be established to obtain metabolite samples a venous line will be placed
In addition an intravenous IV catheter will be inserted into the radial antecubital or other arm or hand vein for injection of tracer Radiopharmaceutical will be injected as a bolus approximately 5mCi for F-18SynVest-1 followed by 5 mL of saline
The whole PET session will last up to 120 min At the time of imaging the subjects will be positioned in the gantry of a PET camera Head alignment will be made relative to the canthomeatal line using projected laser lines whose positions are known with respect to the slice positions of the scanner A head support apparatus will be used to minimize head motion Brain PET data acquisition will begin at the moment of radiotracer injection Images will be acquired using a high-resolution PETCT scanner
MRI Visit
All subjects will undergo a 3T Brain MRI during an MRI visit that may precede or follow the PET scan visit
Pregnancy screening prior to MRI
All women will be queried about their pregnancy status use of contraception and last menstrual period If they are reliably using contraception can state the timing of their last menstrual period and do not believe they could be pregnant the investigators will proceed with the MRI scan without pregnancy testing If they cannot do this then they will undergo a urine pregnancy test If a woman is seeking pregnancy and not using contraception she will undergo a urine pregnancy test
MRI imaging procedures MRI scanning session will be performed at BWH MRI facility at 60 Fenwood Road Boston MA
Several pulse sequences will be performed to image the brain There will be no intravenous contrast used for any of the MRIs
The MRI scan session will take approximately 1 hour
Imaging Data
The following data will be collected on all subjects during scanning sessions
During PET scanning brain images will be acquired in 3-D mode and dynamic acquisition scans will continue for up to 120 minutes A non-diagnostic CT scan will be performed for attenuation correction of PET transmission data at the time of initiation of scanning Blood samples will be collected via an arterial line for radiotracer analysis via the cannula other than the one used for radiotracer injection
Non Imaging Data
MS subjects Expanded Disability Severity Scale EDSS Timed 25-feet walk T25W Modified Fatigue impact Scale Hamilton Depression Rating Scale Wechsler Logical Memory paragraph recall
Healthy Controls Folstein Mini Mental Status Examination Hamilton Depression Rating Scale Wechsler Logical Memory paragraph recall
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None