Ignite Creation Date:
2024-05-06 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 12:51 PM
Study NCT ID:
NCT03632226
Status:
COMPLETED
Last Update Posted:
2019-06-28
First Post:
2018-08-14
Brief Title:
Evaluation of a Novel PET Radioligand to Image OGA
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Evaluation of a Novel PET Radioligand to Image OGA
Status:
COMPLETED
Status Verified Date:
2019-06-25
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:
Background
O-GlcNAcase OGA is a brain enzyme It may play a role in brain disorders like Alzheimer s disease Researchers want to see if a new drug can be used with positron emission tomography PET scans to show OGA better Researchers want to learn more about how it acts in healthy people
Objectives
To test if the new drug 18FOGA-1 can measure its receptor To determine whether the same results occur when scanning a person twice
Eligibility
Healthy adults age 18 and older who are already enrolled in a separate protocol
Design
Some participants will have 1 whole-body PET scan during one 4-hour visit to the clinic Some will have 2-3 brain scans PET and MRI over 2-3 days
For the PET scan a needle will guide a thin plastic tube IV catheter into an arm vein A small amount of radioactive chemical will be injected through the catheter The needle will be removed Only the catheter will be left in the vein
Another IV catheter may be placed to draw blood
Blood pressure heart rate and breathing rate will be measured Participants will have an electrocardiogram
Participants will lie on a bed that slides in and out of the donut-shaped scanner
The scan will last 2-3 hours
For brain PET scan participants will wear a plastic mask to keep their head still
For magnetic resonance imaging MRI scan participants will lie on a table The table slides in and out of the MRI scanner This is a metal cylinder in a strong magnetic field Participants will be in the scanner up to 1 hour
O-GlcNAcase OGA is a brain enzyme It may play a role in brain disorders like Alzheimer s disease Researchers want to see if a new drug can be used with positron emission tomography PET scans to show OGA better Researchers want to learn more about how it acts in healthy people
Objectives
To test if the new drug 18FOGA-1 can measure its receptor To determine whether the same results occur when scanning a person twice
Eligibility
Healthy adults age 18 and older who are already enrolled in a separate protocol
Design
Some participants will have 1 whole-body PET scan during one 4-hour visit to the clinic Some will have 2-3 brain scans PET and MRI over 2-3 days
For the PET scan a needle will guide a thin plastic tube IV catheter into an arm vein A small amount of radioactive chemical will be injected through the catheter The needle will be removed Only the catheter will be left in the vein
Another IV catheter may be placed to draw blood
Blood pressure heart rate and breathing rate will be measured Participants will have an electrocardiogram
Participants will lie on a bed that slides in and out of the donut-shaped scanner
The scan will last 2-3 hours
For brain PET scan participants will wear a plastic mask to keep their head still
For magnetic resonance imaging MRI scan participants will lie on a table The table slides in and out of the MRI scanner This is a metal cylinder in a strong magnetic field Participants will be in the scanner up to 1 hour
Detailed Description:
Objective
Tau a microtubule associated protein regulates axonal structure and function within neurons of the brain Neurofibrillary tangles contain hyper-phosphorylated insoluble tau protein and are a hallmark of Alzheimer s disease AD and other tauopathies Hyperphosphorylation of tau is required for its aggregation into tangles One novel strategy to decrease the phosphorylation of tau is to increase the number of sugar molecules attached to tau with the overly simple mechanism that the presence of the sugar molecules physically blocks phosphorylation In this case the sugar molecule is N-acetyl-Beta-D-glucosamine GlcNAc and increased glycosylation is achieved by inhibiting the enzyme OGA that removes these residues
In collaboration with Eli Lilly our laboratory recently developed 18FOGA-1 a novel PET ligand to image the hydrolase OGA O-GlcNAcase Initial PET scans in monkey demonstrated that 18FOGA-1 is a promising ligand
This protocol is a first-in-human evaluation of 18FOGA-1 and has four phases
1 Phase 1 whole body imaging of one 1 subject with a low injection activity of approximately 2 mCi to confirm that no organ has prominently high uptake of 18FOGA-1
2 Phase 2 kinetic brain imaging in ten 10 subjects with up to 5 mCi injection to quantify OGA in brain relative to concurrent measurement of the parent radioligand in arterial plasma and venous plasma
3 Phase 3 if 18FOGA-1 is successful in Phase 2 in the first couple of subjects we will estimate the radiation-absorbed doses by performing whole body imaging on a total of eight 8 subjects with 5 mCi injection
4 Phase 4 test-retest analysis in twelve 12 subjects of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma 5 mCi per scan and venous plasma
Thus a total of 9 for whole body imaging and 22 for brain imaging
Study Population
Healthy adult female and male volunteers n 22 ages greater than or equal to 18 will undergo brain imaging An additional nine healthy volunteers will undergo whole body dosimetry analysis for a total of 31 healthy volunteers
Design
For quantification of 18FOGA-1 22 healthy controls will undergo brain PET imaging using 18FOGA-1 an arterial line and venous line Of this group of 22 healthy controls having brain PET imaging twelve of them will have a test-retest scan Nine additional subjects will have a whole body PET scan for dosimetry For dosimetry no arterial line will be used
TAB
Outcome Measures
To assess quantitation of OGA with 18FGA-1 we will primarily use two outcome measures namely the identifiability and time stability of distribution volume VT calculated with compartmental modeling In the test-retest study we will calculate the retest variability We will assess whole-body biodistribution and dosimetry of 18FOGA-1 by calculating doses to organs and the effective dose to the body as a whole
Tau a microtubule associated protein regulates axonal structure and function within neurons of the brain Neurofibrillary tangles contain hyper-phosphorylated insoluble tau protein and are a hallmark of Alzheimer s disease AD and other tauopathies Hyperphosphorylation of tau is required for its aggregation into tangles One novel strategy to decrease the phosphorylation of tau is to increase the number of sugar molecules attached to tau with the overly simple mechanism that the presence of the sugar molecules physically blocks phosphorylation In this case the sugar molecule is N-acetyl-Beta-D-glucosamine GlcNAc and increased glycosylation is achieved by inhibiting the enzyme OGA that removes these residues
In collaboration with Eli Lilly our laboratory recently developed 18FOGA-1 a novel PET ligand to image the hydrolase OGA O-GlcNAcase Initial PET scans in monkey demonstrated that 18FOGA-1 is a promising ligand
This protocol is a first-in-human evaluation of 18FOGA-1 and has four phases
1 Phase 1 whole body imaging of one 1 subject with a low injection activity of approximately 2 mCi to confirm that no organ has prominently high uptake of 18FOGA-1
2 Phase 2 kinetic brain imaging in ten 10 subjects with up to 5 mCi injection to quantify OGA in brain relative to concurrent measurement of the parent radioligand in arterial plasma and venous plasma
3 Phase 3 if 18FOGA-1 is successful in Phase 2 in the first couple of subjects we will estimate the radiation-absorbed doses by performing whole body imaging on a total of eight 8 subjects with 5 mCi injection
4 Phase 4 test-retest analysis in twelve 12 subjects of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma 5 mCi per scan and venous plasma
Thus a total of 9 for whole body imaging and 22 for brain imaging
Study Population
Healthy adult female and male volunteers n 22 ages greater than or equal to 18 will undergo brain imaging An additional nine healthy volunteers will undergo whole body dosimetry analysis for a total of 31 healthy volunteers
Design
For quantification of 18FOGA-1 22 healthy controls will undergo brain PET imaging using 18FOGA-1 an arterial line and venous line Of this group of 22 healthy controls having brain PET imaging twelve of them will have a test-retest scan Nine additional subjects will have a whole body PET scan for dosimetry For dosimetry no arterial line will be used
TAB
Outcome Measures
To assess quantitation of OGA with 18FGA-1 we will primarily use two outcome measures namely the identifiability and time stability of distribution volume VT calculated with compartmental modeling In the test-retest study we will calculate the retest variability We will assess whole-body biodistribution and dosimetry of 18FOGA-1 by calculating doses to organs and the effective dose to the body as a whole
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 16-M-0105 | None | None | None |