DepressionPhase 1NCT05703685
[18F]PF-06445974 to Image PDE4B in Major Depressive Disorder Using PET
A Phase 1 study testing Lung scan, Apremilast and 18F-PF-06445974 in people with Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- Lung scan, Apremilast and 18F-PF-06445974
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2023to 11 Apr 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria:
- 18 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 .
Show all 20Show fewer
- 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.
- Able to provide informed consent.
- Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment.
- Be enrolled in 01M0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17M0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies .
- 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.
- Agree to adhere to the lifestyle considerations.
Who cannot join
- 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.
Show all 33Show fewer
- 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).
- 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.
- Use of cytochrome P450 enzyme inducers (e.g. rifampin, phenobarbital, carbamazepine, phenytoin).
- Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigator.
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
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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
Read the 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:
- To determine the optimal length for PDE4B scans with [18F]PF-06445974 PET scans in healthy volunteers
- To measure whole-brain VT of PDE4B in a retest setting.
- To assess the relationship between clinical rating scales and PDE4B binding.
- To measure the blockade of PDE4B radioligand binding in brain after oral administration of apremilast.
- Conditions
- Depression
- Being tested
- Lung scan, Apremilast, 18F-PF-06445974
- Keywords
- PET Imaging, Depression, Phosphodiesterase-4
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lung scanRadiation
Immediately after the brain scan
ApremilastDrug
Oral administration of apremilast
18F-PF-06445974Drug
Injected IV followed by PET scanning
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Radiation: Lung scan; Drug: Apremilast; Drug: 18F-PF-06445974 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure distribution volume
Target quantification
Measured: 36 months
Secondary outcomes (3)
To determine the optimal length
Target quantification
Measured: 36 months
To measure whole-brain distribution volume in retest
Target quantification
Measured: 36 months
measure clinical rating scales and PDE4B binding
Assess the severity of depression
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start22 Jun 2023
- Primary completion3 Oct 2028 (estimated)
- Study completion11 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- 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
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05703685
- Sponsor's protocol ID
- 10000676
- Other IDs
- 000676-M
- Status last verified
- 29 Sep 2026
- First submitted
- 27 Jan 2023
- Last updated
- 1 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 and OpenNeuroPET with consent.
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- [18F]PF-06445974 to Image PDE4B in Major Depressive Disorder Using PET
- ClinicalTrials.gov ID
- NCT05703685
- Acronym / sponsor ID
- 10000676
- Conditions
- Depression
- Keywords
- PET Imaging, Depression, Phosphodiesterase-4
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 22 Jun 2023 (actual)
- Primary completion
- 3 Oct 2028 (estimated)
- Study completion
- 11 Apr 2029 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To determine the optimal length for PDE4B scans with [18F]PF-06445974 PET scans in healthy volunteers
- To measure whole-brain VT of PDE4B in a retest setting.
- To assess the relationship between clinical rating scales and PDE4B binding.
- To measure the blockade of PDE4B radioligand binding in brain after oral administration of apremilast.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| one arm | Other | Radiation: Lung scan, Drug: Apremilast, Drug: 18F-PF-06445974All subjects will receive the same testsGroup D will have a baseline and block with apremilastGroup A \& D will have a lung scan |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria:
- 18 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.
Key exclusion criteria (33 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lung scanImmediately after the brain scan | Radiation | one arm |
| ApremilastOral administration of apremilast | Drug | one arm |
| 18F-PF-06445974Injected IV followed by PET scanning | Drug | one arm |
Primary outcome
To measure distribution volume
Time frame: 36 months
Target quantification
3 secondary outcomes
To determine the optimal length
Time frame: 36 months
To measure whole-brain distribution volume in retest
Time frame: 36 months
measure clinical rating scales and PDE4B binding
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The results will be submitted to ClinicalTrials.gov and OpenNeuroPET with consent.
Related trials for Depression
Active, not recruiting
NYUCI-ES: Psychosocial Intervention to Improve Health Outcomes for Chinese and Korean ADRD Caregivers
Dementia Caregivers, Diabetes
Not yet recruiting
Lung Cancer and Aging: Improving Well-being for Older Adults With Lung Cancer
Lung Cancer
RecruitingPhase 1
Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery
Pain, Postpartum Depression
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Recruiting
Bonding Before Birth: A mHealth Intervention for First-time Expectant Couples
Anxiety, Pregnancy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert B Innis, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lung scan, Apremilast and 18F-PF-06445974 in people with Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tara N Turon, C.R.N.P. ((301) 827-6599, tara.turon@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure distribution volume (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.