Alzheimer s DiseasePhase 1NCT07169630
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
A Phase 1 study testing 18F-PF974 and 18F-florbetaben in people with Alzheimer s Disease and Mild Cognitive Impairment, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Read more about this study
- Who is it for?
- Ages 50 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer s Disease, Mild Cognitive Impairment, Healthy
- What is being tested?
- 18F-PF974 and 18F-florbetaben
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2026to 11 Apr 2030
- Phase
- Phase 1
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 50 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Participants will be referred by a physician with the suspected diagnosis of AD or MCI. However, the PI of this protocol will provide the final diagnosis. For this reason, this protocol will have just one consent form for participants suspected of having either AD or MCI.
- AD and MCI Study Groups:
- Participants must meet all the following criteria:
- Aged 50 or older.
- Be able (or have their Legally Authorized Representative (LAR) be able) to understand the study and be willing to sign a written informed consent document.
- Have been diagnosed by a neurologist or psychiatrist with MCI or AD.
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- Be in good general health as evidenced by medical history and physical examination.
- Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
- Agree to adhere to the lifestyle considerations.
- Healthy Volunteers:
- Participants must meet all the following criteria:
- Aged 50 or older.
- Able to provide informed consent.
- Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
- Have had their radial artery pulse checked for the presence of adequate ulnar collateral flow and the absence of any metal or foreign objects in both wrists.
- Agree to adhere to the lifestyle considerations.
Who cannot join
- Both the study groups will be excluded if they meet any of the following criteria:
- Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
- Participants should not have taken non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of skin products), or immunosuppressants (e.g., methotrexate) must not have been taken in the prior month.
- Have other major neurological or medical diseases that may cause cognitive dysfunction, such as structural brain diseases, metabolic diseases, paraneoplastic syndromes, infectious diseases, or other significant neurological abnormalities.
- Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
- Are unable to travel to the NIH.
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- Have recent exposure to radiation related to research (e.g., PET from other research) that, when combined with this study, would be above the allowable limits.
- Have an inability to lie flat and/or lie still on the camera bed for at least two hours, including claustrophobia, overweight greater than the maximum for the scanner, and uncontrollable behavioral symptoms, which will be screened by an interview with the volunteer and/or caregiver during the screening visit.
- Participants must not have substance use disorder or alcohol use disorder.
- Participants should not be under treatment or previously treated with an amyloid antibody such as lecanemab.
- Are unable to have an MRI scan (e.g., because of pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, shrapnel fragments, or metal fragments in the eye).
- Pregnancy or breast feeding.
- HIV infection.
- Non-English speaking participants.
- Inclusion of children is not appropriate, because this protocol has more than minimal risk from radiation exposure without the possibility of direct benefit.
- Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk. We will not require contraception for this protocol to allow participants autonomy in medical decision-making. However, while we will not require contraception for woman of childbearing potential, we will perform a pregnancy test at screening and prior to all procedures to ensure participants are not pregnant
- Persons with HIV infection are excluded because HIV infection itself may change cAMP signaling.
- Non-English-speaking participants will be excluded from participation in this study because neuropsychological testing is required by this protocol. This testing, which is critical for interpreting study results, has not been validated in other languages or when using a translator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer s Disease (AD) or Mild Cognitive Impairment (MCI)
Background:
About 5 million adults in the United States have age-related brain disorders. These include Alzheimer disease (AD), mild cognitive impairment (MCI), and other dementias. The number of people with these disorders will likely increase as the population ages and life span increases. Inflammation is thought to play a role in AD and MCI. Researchers want to know if an enzyme called PDE4B increases inflammation in people with AD or MCI.
Read more
Objective:
To test whether medical imaging using a new radiotracer ([18F]PF-06445974) can measure PDE4B in the brains of people with AD or MCI.
Eligibility:
People aged 50 years and older with AD or MCI. Healthy volunteers are also needed.
Design:
Participants will have up to 5 clinic visits with 3 imaging scans of the brain.
They will have be screened. They will have a physical exam with blood tests. This will include tests of their heart and nerve function, including memory.
Participants will have 2 positron emission tomography (PET) scans. One will use a standard radiotracer. The other will use the study radiotracer. They will receive each tracer through a tube attached to a needle inserted into a vein. During the scan with the study tracer, participants will have a second tube inserted into a vein in the wrist; this tube will be used to draw blood during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. These visits will take about 6 hours each.
Participants will have 1 magnetic resonance imaging (MRI) scan. They will lie on a bed that slides into a cylinder. This visit will take up to 2 hours....
Read the detailed description
Study Description:
As a biomarker of neuroinflammation, the density of PDE4B is hypothesized to be elevated in individuals with AD or MCI compared to age-matched healthy volunteers (HVs). Participants will receive two positron emission tomography (PET) scans (for PDE4B and for beta-amyloid (A beta)) and one magnetic resonance imaging (MRI) scan of the brain.
Objectives:
Primary Objective:
To determine whether PDE4B radioligand binding is increased in medial temporal lobe of participants with AD or MCI (both A beta positive) compared to age-and sex matched HVs (who are A beta negative)
Exploratory Objective #1:
To determine whether PDE4B binding in the medial temporal lobe is correlated with demographic variables, clinical markers, or biological markers.
Exploratory Objective #2:
To determine whether any region of the brain in individuals with AD or MCI has increased PDE4B binding compared to HVs.
Endpoints:
Primary endpoints: PET measurements of PDE4B; clinical variables, including neuropsychological tests; and biological variables, including plasma concentrations of A(beta)40, A(beta)42, total tau, and Ptau217.
- Conditions
- Alzheimer s Disease, Mild Cognitive Impairment, Healthy
- Being tested
- 18F-PF974, 18F-florbetaben
- Keywords
- 18F-PF-06445974, PET Imaging
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
18F-PF974Drug
Injected IV followed by PET scanning
18F-florbetabenDrug
Injected IV followed by PET scanning
| Study group | Role | What they receive |
|---|---|---|
| One-Arm | Other | All subjects will receive the same tests. Receives: Drug: 18F-PF974; Drug: 18F-florbetaben |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether PDE4B radioligand binding is increased in medial temporal lobe of participants with AD or MCI (both A <= positive) compared to age-and sex matched HVs (who are A <= negative.
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2025
- Study start28 Oct 2026 (estimated)
- Primary completion11 Apr 2029 (estimated)
- Study completion11 Apr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer s DiseaseStudies of the same condition, open and under way.
- 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
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paul A Parcon, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07169630
- Sponsor's protocol ID
- 10002277
- Other IDs
- 002277-M
- Status last verified
- 13 Aug 2026
- First submitted
- 11 Sep 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The results will be submitted to ClinicalTrials.gov