HealthyPhase 1NCT03030391
Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
A Phase 1 study testing PET and MRI in people with Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- PET and MRI
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2017to 16 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 or older.
- Able to give written informed consent.
- Medically and psychiatrically healthy.
- Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate).
Who cannot join
- Any current Axis I diagnosis.
- Clinically significant laboratory abnormalities
- Positive HIV test.
- Unable to have an MRI scan.
- History of neurologic illness or injury with the potential to affect study data interpretation.
- Recent exposure to radiation related to research (i.e. PET from other research) that, when combined with this study, would be above the allowable limits.
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- Inability to lie flat on camera bed for at least two hours.
- Pregnancy or breastfeeding.
- Current substance use disorder based on DSM-5.
- Current use of psychiatric medications.
- NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.
- Exclusion criteria for the dosimetry subjects are the same as reported above, with the exception of MRI contraindications, because an MRI will not be performed in these subjects.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of a Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
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.
Read more
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.
Read the 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:
- 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;
- 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;
- 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;
- 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 (n=22, 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.
- Conditions
- Healthy
- Being tested
- PET, MRI
- Keywords
- Camp, Radiation Absorbed Dose, Compartmental Analysis
- Medical subject headings
- Muscle Cramp
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PETOther
MRIOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantification of 18F-PF-06445974 binding in brain
Measured: 2 hours
Secondary outcomes (1)
Biodistribution of 18F-PF-06445974 in the body.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2017 (estimated)
- Study start10 Jan 2017
- Primary completion16 Mar 2018
- Study completion16 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Masahiro Fujita, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03030391
- Sponsor's protocol ID
- 170041
- Other IDs
- 17-M-0041
- Status last verified
- 16 Mar 2018
- First submitted
- 24 Jan 2017
- Last updated
- 17 Dec 2019
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Novel Positron Emission Tomography (PET) Radiotracer to Image Phosphodiesterase-4B (PDE4B)
- ClinicalTrials.gov ID
- NCT03030391
- Acronym / sponsor ID
- 170041
- Conditions
- Healthy
- Keywords
- Camp, Radiation Absorbed Dose, Compartmental Analysis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 10 Jan 2017
- Primary completion
- 16 Mar 2018 (actual)
- Study completion
- 16 Mar 2018 (actual)
- First posted
- 25 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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;
- 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;
- 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;
- 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 (n=22, 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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 or older.
- Able to give written informed consent.
- Medically and psychiatrically healthy.
- Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate).
Key exclusion criteria (12 listed)
- Any current Axis I diagnosis.
- Clinically significant laboratory abnormalities
- Positive HIV test.
- Unable to have an MRI scan.
- History of neurologic illness or injury with the potential to affect study data interpretation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET | Other | – |
| MRI | Other | – |
Primary outcome
Quantification of 18F-PF-06445974 binding in brain
Time frame: 2 hours
1 secondary outcome
Biodistribution of 18F-PF-06445974 in the body.
Time frame: 2 hours
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Masahiro Fujita, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PET and MRI in people with Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantification of 18F-PF-06445974 binding in brain (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019.