[11C]-(R)-Rolipram to Measure cAMP Signaling Before and After Ketamine

NCT05522673 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 10000824000824-M
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Major depressive disorder (MDD) may have many underlying causes. One theory is that brain cells with low levels of a molecule called cyclic AMP (cAMP) may cause depression. A drug called ketamine may increase the levels of cAMP in a person's brain cells. Objective: To find out if administering ketamine to people with depression affects cAMP levels in their brains. Eligibility: People aged 18 to 70 with MDD who are enrolled in another NIH study that uses ketamine. Design: Participants will visit the NIH clinic 5 times in up to 6 weeks. Some of the visits may be spread out over more than 1 day. Participants will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They will have a psychiatric evaluation. They will answer questions about their family history and mental health. Participants will have a positron emission tomography (PET) scan. A small amount of a radioactive drug will be injected into a vein in their arm. Participants will lie on a bed that slides in and out of a doughnut-shaped machine that records images of their brains. They will have their heads in a holder to prevent movement. Each scan will last up to 2 hours. After their first PET scan, participants will receive ketamine in a different study they are enrolled in. Then they will come back for another PET scan with the radioactive drug. Participants will also have another scan called an MRI. They will lie on a table that slides into a metal tube. They will lie still for up to an hour....

Conditions

Depression

Keywords

PET Imaging; Inflammation; Ketamine; Depression

Outcome Measures

Primary Outcomes (1)

• Whole Brain Total Distribution Volume (VT)

  Participants received 11C-R-Rolipram during PET scan and were scanned for 90 minutes with arterial blood sampling. Volume of distribution was calculated using two-tissue compartmental modeling. Participants had one PET scan pre-Ketamine and a second PET scan post-Ketamine administration.

  90 minutes after injection of 11C-R-Rolipram

Secondary Outcomes (2)

• Measure of Level of Depression Using Montgomery-Åsberg Depression Rating Scale (MADRS)

  Within two weeks of start of study (Pre) and within 7 days of Ketamine infusion (Post)

• Measure of Level of Depression Using the Hamilton Depression (HAM-D) Rating Scale

  Within two weeks of start of study (Pre) and within 7 days of Ketamine infusion (Post)

Study Arms (1)

Subjects with major depression disorder (MDD)

OTHER

Participants with major depressive disorder received 20 mCi of \[11C\](R)-rolipram intravenously for two PET scans, prior to and after ketamine infusion as well as brain MRI

Drug: 11(R)-rolipram

Interventions

11(R)-rolipram DRUG

Injected IV followed by PET scanning

Subjects with major depression disorder (MDD)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients:
• In order to be eligible for this study, MDD participants must meet all of the following criteria:
• Be male or female, aged 18 to 70 years old.
• Female participants of childbearing potential must be using a medically acceptable means of contraception.
• Participants must be in good general health as evidenced by medical history and physical examination.
• 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'.
• Participants must be enrolled in the ketamine arms of protocols 19-M-0107 'Ketamine and AMPA', 17-M-0060 'Neuropharmacology of Ketamine', or 15-M-0188 'Neurobiology of Suicide'.
• 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 two weeks of study entry.
• Participants with stable medical conditions as assessed by their primary care provider (PCP) and/or in-house clinician are permitted to join the study.
• Patients must qualify for ketamine administration, usually defined as lack of response to two adequate lifetime antidepressant trials, with \[at least\] one in the current major depressive episode, operationally defined using the Antidepressant Treatment History Form (ATHF); a failed adequate trial of ECT \[or TMS\] would count as an adequate antidepressant trial.
• 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.

You may not qualify if:

• 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; acute care panel \[Na, K, Cl, CO2, creatinine, glucose, urea nitrogen); hepatic panel (alkaline phosphatase, alanine transaminase (ALT), aspartate aminotransferase (\[AST), bilirubin total, and bilirubin direct\]; mineral panel (albumin, calcium, magnesium, phosphorus); glucose; prothrombin and partial prothrombin tests.
• Current psychotic features, a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-5.
• Participants who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
• 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).
• 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 National Institute of Mental Health (NIMH) staff or an NIH employee who is a subordinate/relative/co-worker of the investigators.
• Pregnancy
• HIV infection

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depression; Inflammation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study was prematurely terminated due to low recruitment

Results Point of Contact

• Title: Dr. Robert Innis
• Organization: National Institute of Mental Health (NIMH)

robert.innis@nih.gov

301-594-1368

Study Officials

• Robert B Innis, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: August 31, 2022
• Study Start: February 8, 2023
• Primary Completion: February 8, 2023
• Study Completion: January 30, 2024
• Last Updated: March 5, 2024
• Results First Posted: March 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)