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

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ClinicalTrials.gov Identifier: NCT04582916
Recruitment Status : Recruiting
First Posted : October 12, 2020
Last Update Posted : November 26, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

Background:

Researchers developed [11C]MC1, a radioligand for cyclooxygenase-2 (COX-2). COX-2 is an enzyme induced in the brain during inflammation. Researchers want to see if COX-2 is measurable in the brains of people with MDD who are having a major depressive episode (MDE).

Objective:

To learn if COX-2 is detectable in the brains of people with MDD who are having an MDE.

Eligibility:

Healthy people ages 18 70 years old with MDD.

Design:

Participants will be screened under protocol 01-M-0254. They will have a medical history, physical exam, and psychiatric evaluation. They will have blood tests. They will have an electrocardiogram (EKG) to measure heart function.

Participants will have a magnetic resonance imaging (MRI) scan of the brain. MRI uses a strong magnetic field and radio waves to take pictures. The MRI scanner is a metal cylinder. Participants will lie on a table that slides in and out of the cylinder. The machine makes loud knocking noises. Participants will get earplugs or earmuffs.

Participants will have 2 PET scans of the brain. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be shaped to fit their head. An intravenous (IV) catheter will be put into a vein of the arm. A small amount of the radioactive chemical [11C]MC1 will be injected through the IV catheter. Another catheter will be put into an artery at the wrist or elbow crease and used to draw blood. Participants vital signs will be recorded. They will have EKGs and give urine samples. Participation lasts 1 to 2 weeks.


Condition or disease Intervention/treatment Phase
Depression Drug: 11C-MCI Drug: Drug Phase 1

Detailed Description:

Study Description: This pilot/exploratory study will examine whether cyclooxygenase 2 (COX-2) is detectable in the brain of individuals with major depressive disorder (MDD).

Objectives:

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

Endpoints: Primary Endpoint: Calculation of COX-2 density from [11C]MC1 PET scans, using baseline scans and scans after blockade with celecoxib. Secondary Endpoints: 1) the relationship between peripheral markers of inflammation and COX binding

2) the relationship between clinical rating scales and COX binding

Study Population: Sixteen (16) medication-free participants with MDD will be recruited. 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.

Phase: 1

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

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Phase 1 Study: PET Imaging of Cyclooxygenase in Participants With Major Depressive Disorder (MDD)
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : May 29, 2023
Estimated Study Completion Date : August 29, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
One Arm
All subject receive the same tests
Drug: 11C-MCI
Injected IV followed by PET scanning

Drug: Drug
COX-2 inhibitor




Primary Outcome Measures :
  1. Measure the concentration of radioligands [ Time Frame: 36 months ]
    Tracer binding level


Secondary Outcome Measures :
  1. measure peripheral markers of inflammation and COX binding [ Time Frame: 36 months ]
    Assess the severity of depression and/or anxiety

  2. measure clinical rating scales and COX binding [ Time Frame: 36 months ]
    Assess the severity of depression and/or anxiety



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

In order to be eligible for this study, MDD participants must meet all of the following criteria:

  1. Be male or female, aged 18 to 70 years old.
  2. Female participants of childbearing potential must be using a medically acceptable means of contraception.
  3. Participants must be in good general health as evidenced by medical history and physical examination.
  4. Each participant must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
  5. 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' (PI: Carlos A. Zarate Jr).
  6. Participants must fulfill DSM-5 criteria for major depression (MDD) without psychoticfeatures, as based on clinical assessment and structured diagnostic interview (SCID-P).
  7. Participants must have an initial score on the MADRS greater than or equal to 18 or HAM-D greater than or equal to 15 within one week of study entry.
  8. Participants must be experiencing an MDE lasting at least four weeks.
  9. Participants must be medication-free for at least two weeks (5 weeks for aripirazole, brexpiprazole, fluoxetine) prior to first screen visit. Medications will not be discontinued for the purpose of this study.
  10. Participants with stable medical conditions as assessed by their primary care provider (PCP) and/or in-house clinician are permitted to join the study.
  11. All MDD participants must have a PCP or psychiatrist in the community.
  12. 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.
  13. Participants must agree to adhere to the lifestyle considerations.

EXCLUSION CRITERIA:

Participants with MDD who meet any of the following criteria will be excluded from participation in this study:

  1. Clinically significant abnormalities on EKG or laboratory testing. This includes CBC; acute care panel (Na, K, Cl, CO2, creatinine, glucose, urea nitrogen); hepatic panel (alkaline phosphatase, ALT, AST, bilirubin total, and bilirubin direct); mineral panel (albumin, calcium, magnesium, phosphorus); glucose; prothrombin and partial prothrombin tests; HIV blood test; and pregnancy test for women of childbearing potential.
  2. 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, anti-inflammatory drugs (except for study medication celecoxib), antipsychotics, anxiolytics, psychotropic drugs not otherwise specified (including herbal products), and sedatives/hypnotics.
  3. Participants should not have taken NSAIDs for two weeks prior to the PET scan. Aspirin, corticosteroids, or immunosuppressants (e.g. methotrexate) must not have been taken in the prior month.
  4. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-5.
  5. 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 used illicit substances or known drugs of abuse (except for caffeine or nicotine) in the two weeks prior to screening and must have a negative alcohol and drug urine test at screening.
  6. Participants who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
  7. Participants who have a history of aggressive behavior towards others.
  8. 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).
  9. Are unable to travel to the NIH.
  10. 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.
  11. 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.
  12. 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.
  13. Be NIMH staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.

EXCLUSION OF CHILDREN:

Because this protocol has more than minimal risk from radiation exposure without possibility of direct benefit, inclusion of children is not appropriate.

EXCLUSION OF PREGNANT OR BREASTFEEDING WOMEN:

Pregnant women will be excluded because this protocol involves exposure to ionizing radiation. Lactating women will be excluded because radioisotopes may be excreted in milk.

EXCLUSION OF PARTICIPANTS WHO ARE HIV POSITIVE:

Persons with HIV infection are excluded because HIV infection itself may cause neuroinflammation, and we wish to specifically study the effect of depression on neuroinflammation.

EXCLUSION OF NON ENGLISH SPEAKING PARTICIPANTS:

Non-English-speaking participants will be excluded from participation in this study because neuropsychological testing is required by this protocol. This testing, which is critical for interpreting study results, has not been validated in other languages or when using a translator.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04582916


Contacts
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Contact: Maria M Araneta (301) 443-6602 maria.araneta@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)
Additional Information:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT04582916    
Other Study ID Numbers: 200157
20-M-0157
First Posted: October 12, 2020    Key Record Dates
Last Update Posted: November 26, 2020
Last Verified: October 5, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
PET Imaging
Inflammation
Cyclooxygenase-2
Depression
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders