Depression
Conditions
Keywords
PET Imaging, Inflammation, Cyclooxygenase-2, Depression
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 the levels of COX-1 (measured as distribution volume VT) are elevated in the brain of two groups of mood disorders patients undergoing MDE relative to the control group. Objective: To determine whether COX-1 and COX-2 are detectable in the brains of individuals with MDD experiencing a major depressive episode (MDE). Eligibility: People aged 18-70 years with MDD and Healthy Volunteers aged 18 70 years. Design: Group A: MDD participants will be studied with the same dose of \[11C\]MC1 before and after administration of 600 mg celecoxib; the study is neither randomized nor placebo-controlled. Group B: MDD participants, both medicated and unmedicated, will be studied with \[11C\]PS13 and compared to healthy volunteers.. https://nimhcontent.nimh.nih.gov/start/surveys/?s=TJW4RA4WN3LDD988
Detailed 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
Interventions
DRUG11C-MCI
Injected IV followed by PET scanning
DRUG11CPS13
Injected IV followed by PET scanning
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: Patients: In order to be eligible for this study, MDD participants must meet all of the following criteria: 1. 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 01M0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Participants . 6. Participants must fulfill DSM-5 criteria for major depression (MDD) without psychotic features, 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. Unmedicated participants in both Groups 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 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. 11. 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: 1. Aged 18 to 70 years old. 2. Female participants of childbearing potential must be using a medically acceptable means of contraception. 3. Able to provide informed consent. 4. Be in good general health, as evidenced by medical history and physical examination, and have no cognitive impairment. 5. 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 . 6. 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. 7. 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 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. 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. Medicated participants in Group B may continue their therapy. 3. Participants should not have taken Non-Steroidal Anti-Inflammatory Drug (NSAID)s for two weeks prior to the PET scan. Aspirin, corticosteroids (with the exception of topical steroids), 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 caffeinei 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure the concentration of radioligands | 36 months | Tracer binding level |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| measure peripheral markers of inflammation and COX binding | 36 months | Assess the severity of depression and/or anxiety |
| measure clinical rating scales and COX binding | 36 months | Assess the severity of depression and/or anxiety |
Countries
United States
Contacts
CONTACTTara N Turon, C.R.N.P.
CONTACTRobert B Innis, M.D.
PRINCIPAL_INVESTIGATORRobert B Innis, M.D.
National Institute of Mental Health (NIMH)
Outcome results
None listed