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

Phase 1
Recruiting
Conditions
Depression
Interventions
Radiation: Lung scan
Drug: Apremilast
Drug: 18F-PF-06445974
Registration Number
NCT05703685
Lead Sponsor
National Institute of Mental Health (NIMH)
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

Detailed Description

Study Description:

This study will examine whether phosphodiesterase 4B (PDE4B) can be accurately quantified in the human brain and whether it is reduced in the brain of individuals with major depressive disorder (MDD).

Objectives:

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.

Endpoints:

Primary Endpoint: measurement of PDE4B density (distribution volume VT) in the brains of individuals with MDD compared to healthy volunteers

Secondary endpoints:

1. To determine the optimal length for PDE4B scans with \[18F\]PF-06445974 PET scans in healthy volunteers

2. To measure whole-brain VT of PDE4B in a retest setting.

3. To assess the relationship between clinical rating scales and PDE4B binding.

4. To measure the blockade of PDE4B radioligand binding in brain after oral administration of apremilast.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
108
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
one armLung scanAll subjects will receive the same testsGroup D will have a baseline and block with apremilastGroup A \& D will have a lung scan
one armApremilastAll subjects will receive the same testsGroup D will have a baseline and block with apremilastGroup A \& D will have a lung scan
one arm18F-PF-06445974All subjects will receive the same testsGroup D will have a baseline and block with apremilastGroup A \& D will have a lung scan
Primary Outcome Measures
NameTimeMethod
To measure distribution volume36 months

Target quantification

Secondary Outcome Measures
NameTimeMethod
To measure whole-brain distribution volume in retest36 months

Target quantification

measure clinical rating scales and PDE4B binding36 months

Assess the severity of depression

To determine the optimal length36 months

Target quantification

Trial Locations

Locations (1)

National Institutes of Health Clinical Center

🇺🇸

Bethesda, Maryland, United States

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