[18F]PF-06445974 to Image PDE4B in Major Depressive Disorder Using PET

Recruiting now · Phase 1

Conditions studied: Depression

In brief

Background: Major depressive disorder (MDD) is a psychiatric condition. People with MDD have occasional bouts of depressive symptoms; these bouts are called major depressive episodes (MDEs). Researchers want to know if people having MDEs have lower levels of an enzyme called PDE4B in their brains. Primary Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary Objectives: To determine the optimal length of scanning and the retest variability and reliability of \[18F\]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. To measure if PDE4B radioligand binding can be blocked by taking apremilast. Eligibility: People aged 18-70 years with MDD. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. Some participants may have a psychiatric assessment; they will answer questions about their state of mind and related topics. Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that slides into a metal cylinder. Participants will have a positron emission tomography (PET) scan. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer (\[18F\]PF-06445974) will be injected through the catheter. Participants will lie on a table that slides into a doughnut-shaped machine. The scan will last up to 4 hours with a 15-minute break. Participants blood pressure, heart rate, and breathing will be monitored before, during, and after the PET scan. A second catheter will be inserted in the artery of the wrist so blood can be drawn during the scan. Some participants may return for a second PET scan; have a lung scan or receive apremilast. https://nimhcontent.nimh.nih.gov/start/surveys/?s=KE88DXXPLDFHHTF8

Key facts

Study ID: NCT05703685
Run by: National Institute of Mental Health (NIMH)
People needed: 108
Starts: 2023-06-22
Expected to finish: 2029-04-11
Last updated by the study team: 2026-07-02

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

Participants with MDD who meet any of the following criteria will be excluded from participation in this study:
Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen). Any lab value that is two-times the upper limit or even lower values in the investigator s judgment. Creatinine level >1.3 mg/dL.
Participants must be free of all prohibited medications for at least two weeks (5 weeks for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications include antidepressants, antipsychotics, anxiolytics, psychotropic drugs not otherwise specified
(including herbal products), and sedatives/hypnotics.
Current psychotic features, a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-5.
Participants with a history of psychiatric inpatient hospitalization within the past year.
Participants with a history of DSM-5 substance use disorder (except for caffeine or nicotine dependence) within the preceding three months. In addition, participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function of daily life.
Participants who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
Participants with suicidal ideation within the past 6 months.
Participants with suicidal behavior within the past 12 months.
Participants who have a history of aggressive behavior towards others.
Participants who have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).
HIV infection.
Pregnancy.
Are unable to travel to the NIH.
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 participant during the screening visit.
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.
Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.
Healthy controls who meet any of the following criteria will be excluded from participation in this study:
Clinically significant abnormalities on EKG or laboratory testing. This includes CBC and acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen).
Participants must be free of all prohibited medications or at least two weeks (5 weeks for aripiprazole, brexpiprazole, fluoxetine) prior to screen visit. These medications include antidepressants, antipsychotics, anxiolytics, psychotropic drugs not otherwise specified (including herbal products), and sedatives/hypnotics.
Participants with a history of DSM-5 substance use disorder (except for caffeine or nicotine dependence) within the preceding three months. In addition, participants must not have substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use impairs function of daily life.
Participants who have a history of major depressive disorder.
Participants who have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe (e.g., an active infection or untreated malignancy).

Where it is running

National Institutes of Health Clinical Center — Bethesda, Maryland, United States (enrolling)

Full record on ClinicalTrials.gov

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