PET Imaging of Cyclooxygenase in Participants With Major Depressive Disorder (MDD)

  • STATUS
    Recruiting
  • End date
    Aug 29, 2023
  • participants needed
    64
  • sponsor
    National Institute of Mental Health (NIMH)
Updated on 10 October 2021
anxiety
depressive disorder
scid
depressed mood
depressive episode
fluoxetine
Accepts healthy volunteers

Summary

Purpose: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE).

Endpoints

Primary Endpoint:

Group A - Calculation of COX-2 density from [11C]MC1 PET scans, using baseline scans and scans after blockade with celecoxib.

Group B - Calculation of the density of COX-1 using [11C]PS13 in healthy volunteers and depressed subjects.

Secondary Endpoints:

  1. the relationship between peripheral markers of inflammation and COX binding
  2. the relationship between clinical rating scales and COX binding

Study Design: Group A Sixteen (16) medication-free participants with MDD; Group B Three groups of 16 subjects each will be studied: 1) Medicated MDD, 2) Unmedicated MDD and 3) healthy volunteers. Participants may be male or female. They must be between 18 and 70 years old. Individuals may be recruited from anywhere but, for those participating in the outpatient study, most are expected to come from the Washington DC metropolitan area. MDD participants must be in good medical health and provide informed consent.

Data acquisition of [11C]MC1 and [11C]PS13:

  1. Dynamic 3D PET brain scan on PET/CT.
  2. One venous line for radioligand injection.
  3. Arterial line for blood sampling.
  4. Transmission (CT) scan will be performed to measure and correct for attenuation.
  5. Injection of 20 mCi of [11C]MC1 or [11C]PS13.
  6. Emission scans on PET/CT or PET scanner. Emission scan for about 90 min (possibly up to 2h). Frame information: 6 frames 30 sec each, 3 frames 1 min each, 2 frames 2 min each, and remaining frames of 5 min each.
  7. Vital signs (blood pressure, pulse, and respiratory rate) and ECG (either 3 or 12 lead) will be recorded within three hours of tracer injection, in the middle, and after the PET scan.
  8. We will take the two [11C]MC1 scans preferably in same day. They should be separated by at least 2.5 hours

Blood analysis in [11C]MC1 and [11C]PS13:

  1. Measurement of whole blood, plasma activity, and metabolite levels in all phases: MIB/NIMH.
  2. Measurement of whole blood activity by PET Department is not required in any phase.

Administration of celecoxib: In these scans, specific binding of [11C]MC1 to COX-2 in the brain will be verified by a pre-blocking study using celecoxib (600 mg PO). Participants will be encouraged to have a light meal prior to PET studies with blockade by celecoxib. After oral administration, the plasma concentration peaks at about two hours (Paulson et al. 2001). Thus, we will administer celecoxib about two hours before the second PET scan.

Safety monitoring by MIB/NIMH:

  1. Pre-scan labs within 24 hours prior to injection: Urine pregnancy test (woman of child bearing potential), CBC, acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen), hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct), glucose, mineral panel (albumin, calcium, magnesium, phosphorus).
  2. C-reactive protein (CRP) will be measured in the pre-PET blood sample to assess overall inflammatory status in periphery.
  3. Data for safety monitoring will be recorded at three timepoints: no more than three hours before injection, about the middle of the PET scan, and after the PET scan. Recorded data included: blood pressure, pulse, respiratory rate, and EKG (either 3- or 12-lead).
  4. Post-scan labs: CBC, acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen), hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct), glucose, mineral panel (albumin, calcium, magnesium, phosphorus).
  5. Pregnancy Tests: For women of childbearing potential, urine pregnancy testing will be done within the 24 hours prior to any MRI or PET scan. If the pregnancy test is positive, PET and MRI will not be done, and the subject will be taken off the protocol.
  6. Follow-up Procedures: Subjects will be contacted one to three business days after each PET scan to determine whether they have had any untoward sequelae.

Description

Study Description: This study will examine whether cyclooxygenase 1 (COX-1) and cyclooxygenase-2 (COX-2) are detectable in the brain of individuals with major depressive disorder (MDD).

Objectives: Primary Objective: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE).

Endpoints: Primary Endpoints: Group A - Calculation of COX-2 density from [11C]MC1 PET scans, using baseline scans and scans after blockade with celecoxib. Group B - Calculation of the density of COX-1 using [11C]PS13

Secondary Endpoints, common to both groups:

  1. the relationship between peripheral markers of inflammation and COX binding;
  2. the relationship between clinical rating scales and COX binding

Study Population: Group A) Sixteen (16) medication-free participants with MDD;

Group B) Three groups of 16 subjects each will be studied: 1) Medicated MDD, 2) Unmedicated MDD and 3) healthy volunteers. Participants may be male or female. They must be between 18 and 70 years old. Individuals may be recruited from anywhere but, for those participating in the outpatient study, most are expected to come from the Washington DC metropolitan area. MDD participants must be in good medical health and provide informed consent.

Description of Sites/Facilities Enrolling Participants: Screening and PET imaging will be performed at the NIH Clinical Center.

Description of Study Intervention: Group A - Participants will be intravenously injected with 20 mCi of [11C]MC1 twice, once at baseline and once after blockade by celecoxib.

Group B - Subjects will be intravenously injected once with 20 mCi of [11C]PS13 and

For both groups, participants will also have a radial artery catheter(s) inserted to measure radioligand concentration before each scan. Participants will also have a brain MRI to provide anatomic orientation for the PET scans.

Study Duration: 36 months

Participant Duration: One to two weeks, depending on the participant's availability and investigators' overall access to MRI and PET cameras.

Details
Condition Endogenous depression, Depression, Depression (Major/Severe), Depression (Adolescent), Depression (Pediatric), Depression (Adult and Geriatric), Depression (Treatment-Resistant), Depressed, depressive disorder, depressed mood, miserable, depressive disorders
Treatment drug, 11C-MCI, 11CPS13
Clinical Study IdentifierNCT04582916
SponsorNational Institute of Mental Health (NIMH)
Last Modified on10 October 2021

Eligibility

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note