Ignite Creation Date:
2024-05-06 @ 9:38 AM
Last Modification Date:
2024-10-26 @ 12:17 PM
Study NCT ID:
NCT03030391
Status:
TERMINATED
Last Update Posted:
2019-12-17
First Post:
2017-01-24
Brief Title:
Novel Positron Emission Tomography PET Radiotracer to Image Phosphodiesterase-4B PDE4B
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Evaluation of a Novel Positron Emission Tomography PET Radiotracer to Image Phosphodiesterase-4B PDE4B
Status:
TERMINATED
Status Verified Date:
2018-03-16
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
The new drug 18F-PF-06445974 has a little radioactivity This can be seen by a positron emission tomography PET scan The drug helps researchers see a protein PDE4B in the brain Looking at PDE4B in the living brain might show how it is involved in psychiatric and neurological disorders One part of the study will look at how the study drug is distributed in the brain Another part will study how brain measures vary
Objectives
To measure the protein PDE4B in the brain To test how a new radioactive chemical 18F-PF-06445974 is distributed in the body
Eligibility
Healthy adults ages 18 and older
Design
Participants will have 1-3 visits over a year Each will be 2-5 hours
Women will have a pregnancy test each time
The new drug 18F-PF-06445974 has a little radioactivity This can be seen by a positron emission tomography PET scan The drug helps researchers see a protein PDE4B in the brain Looking at PDE4B in the living brain might show how it is involved in psychiatric and neurological disorders One part of the study will look at how the study drug is distributed in the brain Another part will study how brain measures vary
Objectives
To measure the protein PDE4B in the brain To test how a new radioactive chemical 18F-PF-06445974 is distributed in the body
Eligibility
Healthy adults ages 18 and older
Design
Participants will have 1-3 visits over a year Each will be 2-5 hours
Women will have a pregnancy test each time
Detailed Description:
Objective
Phosphodiesterase type 4 PDE4 terminates signal transduction of guanine nucleotidebinding proteins G-protein-coupled receptors by metabolizing the second messenger 3 5 - cyclic adenosine monophosphate cAMP PDE4 is selective to cAMP over cyclic guanosine monophosphate PDE4 has four isozymes A B C and D and basic studies indicate that type B PDE4B plays a key role in cognitive function and neuroinflammation Thus PDE4B inhibitors would be expected to improve cognitive function and have anti-inflammatory effects Pfizer has developed a new PET ligand 18F-PF-06445974 to selectively image PDE4B the ligand has shown promising results in non-human primates
This protocol covers four phases
1 Phase 1 whole body imaging of one subject with a low injection activity of 2 mCi to confirm that no organ has prominently high uptake of 18F-PF-06445974
2 Phase 2 kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain relative to concurrent measurement of the parent radioligand in arterial plasma
3 Phase 3 if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects we will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi injection
4 Phase 4 test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma 5 mCi per scan
Study Population
Healthy adult female and male volunteers n22 ages 18 or older will undergo brain imaging An additional eight healthy volunteers will undergo whole body dosimetry analysis for a total of 30 healthy volunteers
Design
For quantification of 18F-PF-06445974 22 healthy controls will undergo brain PET imaging using 18F-PF-06445974 and an arterial line Some of them will have a test-retest scan Eight additional subjects will have a whole body PET scan for dosimetry For dosimetry no arterial line will be used
Outcome Measures
To assess quantitation of PDE4B with 18F-PF-06445974 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 18F-PF-06445974 by calculating doses to organs and effective dose to the body
Phosphodiesterase type 4 PDE4 terminates signal transduction of guanine nucleotidebinding proteins G-protein-coupled receptors by metabolizing the second messenger 3 5 - cyclic adenosine monophosphate cAMP PDE4 is selective to cAMP over cyclic guanosine monophosphate PDE4 has four isozymes A B C and D and basic studies indicate that type B PDE4B plays a key role in cognitive function and neuroinflammation Thus PDE4B inhibitors would be expected to improve cognitive function and have anti-inflammatory effects Pfizer has developed a new PET ligand 18F-PF-06445974 to selectively image PDE4B the ligand has shown promising results in non-human primates
This protocol covers four phases
1 Phase 1 whole body imaging of one subject with a low injection activity of 2 mCi to confirm that no organ has prominently high uptake of 18F-PF-06445974
2 Phase 2 kinetic brain imaging with up to 5 mCi injection to quantify PDE4B in brain relative to concurrent measurement of the parent radioligand in arterial plasma
3 Phase 3 if 18F-PF-06445974 is successful in Phase 2 in the first couple of subjects we will estimate the radiation-absorbed doses by performing whole body imaging with 5 mCi injection
4 Phase 4 test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma 5 mCi per scan
Study Population
Healthy adult female and male volunteers n22 ages 18 or older will undergo brain imaging An additional eight healthy volunteers will undergo whole body dosimetry analysis for a total of 30 healthy volunteers
Design
For quantification of 18F-PF-06445974 22 healthy controls will undergo brain PET imaging using 18F-PF-06445974 and an arterial line Some of them will have a test-retest scan Eight additional subjects will have a whole body PET scan for dosimetry For dosimetry no arterial line will be used
Outcome Measures
To assess quantitation of PDE4B with 18F-PF-06445974 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 18F-PF-06445974 by calculating doses to organs and effective dose to the body
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 |
|---|---|---|---|
| 17-M-0041 | None | None | None |