A Phase 1 interventional study of 18F-PF974 and 18F-florbetaben in Alzheimer s Disease, Mild Cognitive Impairment and Healthy, sponsored by National Institute of Mental Health (NIMH). Recruiting at 1 site in United States. Open to participants aged 50 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by National Institute of Mental Health (NIMH) · Phase 1, Interventional, and Diagnostic
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.
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....
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.
3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.
This study's planned enrollment of 90 is above the median of 64 across 2,794 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →National Institute of Mental Health (NIMH) is the lead sponsor of 367 studies on the registry; 45 are open to participants now.
Of its 25 completed or terminated interventional studies of FDA-regulated products, 24 (96%) have results posted.
Counted across the registry records on this site, refreshed daily.
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:
Healthy Volunteers:
Participants must meet all the following criteria:
EXCLUSION CRITERIA:
Both the study groups will be excluded if they meet any of the following criteria:
Exclusion of Children:
Inclusion of children is not appropriate, because this protocol has more than minimal risk from radiation exposure without the possibility of direct benefit.
Exclusion of Pregnant or Breastfeeding Women:
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 for this protocol to allow participants autonomy in medical decision-making. However, while we will not require contraception for woman of , we will perform a pregnancy test at screening and prior to all procedures to ensure participants are not pregnant
Exclusion of Participants who are HIV Positive:
Persons with HIV infection are excluded because HIV infection itself may change cAMP signaling.
Exclusion of Non-English-Speaking Participants:
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All subjects will receive the same tests.
Drug: 18F-PF974 · Drug: 18F-florbetaben
Injected IV followed by PET scanning
Injected IV followed by PET scanning
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.
Time frame: 48 months
Plan to share: Yes — The results will be submitted to ClinicalTrials.gov
Supporting information: Study protocol
Time frame: 18 months after closure of protocol.
Access criteria: BTRIS
Start is estimated for Nov 2026; primary completion for Apr 2029, 28 months later.
Of 54 non-industry phase 1 interventional studies under Cognitive Dysfunction, half reached primary completion within 43 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 64. This study's planned 28 months is below that.
Counting every sponsor, half of 80 studies reached it within 27 months; a quarter within 13 and three quarters within 49.
Start moved 32 times since we started tracking on Sep 25, 2026: Sep 2026 → Nov 2026, last on Nov 10, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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