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

NCT05703685 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000676000676-M
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Depression

Keywords

PET Imaging; Depression; Phosphodiesterase-4

Outcome Measures

Primary Outcomes (1)

• To measure distribution volume

  Target quantification

  36 months

Secondary Outcomes (3)

• To determine the optimal length

  36 months

• To measure whole-brain distribution volume in retest

  36 months

• measure clinical rating scales and PDE4B binding

  36 months

Study Arms (1)

one arm

OTHER

All subjects will receive the same testsGroup D will have a baseline and block with apremilastGroup A \& D will have a lung scan

Radiation: Lung scan; Drug: Apremilast; Drug: 18F-PF-06445974

Interventions

Lung scan RADIATION

Immediately after the brain scan

one arm

Apremilast DRUG

Oral administration of apremilast

one arm

18F-PF-06445974 DRUG

Injected IV followed by PET scanning

one arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria:
• to 70 years of age.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.
• Be in good general health as evidenced by medical history and physical examination. Stable medical conditions as assessed by their primary care provider (PCP) and/or in-house clinician are permitted to join the study.
• Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
• All participants must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants .
• Participants must fulfill DSM-5 criteria for major depression (MDD) without psychotic features, as based on clinical assessment and structured diagnostic interview (SCID-P).
• Participants must have an initial score on the MADRS \>= 18 or HAM-D \>= 15 within one week of study entry.
• Participants must be experiencing an MDE lasting at least four weeks.
• All MDD participants must have a PCP or psychiatrist in the community.
• Participants must have 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.
• Participants must agree to adhere to the lifestyle considerations.
• Healthy Controls: In order to be eligible to participate in this study, control subjects must meet all of the following criteria:
• Aged 18 to 70 years old.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.

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 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.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depression

Interventions

apremilast

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tara N Turon, C.R.N.P.

CONTACT

(301) 827-6599; tara.turon@nih.gov

Robert B Innis, M.D.

CONTACT

(301) 594-1368; robert.innis@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2023
• First Posted: January 30, 2023
• Study Start: June 22, 2023
• Primary Completion (Estimated): October 3, 2028
• Study Completion (Estimated): April 11, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04-22

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 18 months after closure of protocol
• Access Criteria: BTRIS

Locations

US (1)