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

Phase 1

Terminated

Conditions: Depression

Interventions: Drug: 11(R)-rolipram

Registration Number: NCT05522673

Lead Sponsor: National Institute of Mental Health (NIMH)

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....

Detailed Description: Study Description:

This study will test the effects of ketamine infusion on the cAMP system in human brain to determine if ketamine mediates its antidepressant effects at least in part due to modulation of cAMP signaling.

Objectives:

Primary Objective: To determine if ketamine infusions in depression causes increases in cAMP signaling as measured by \[11C\](R)-rolipram binding.

Secondary Objectives: To determine if increases in \[11C\](R)-rolipram correlate with symptomatic improvement in major depressive symptoms.

Endpoints:

Primary Endpoint: measurement of PDE4 density (volume of distribution VT) in brains of individuals with major depressive disorder (MDD) before and after administration of ketamine.

Secondary Endpoints: Clinical rating scales of depression, including MADRS, HAM-D.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Subjects with major depression disorder (MDD)	11(R)-rolipram	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

Primary Outcome Measures

Name	Time	Method
Whole Brain Total Distribution Volume (VT)	90 minutes after injection of 11C-R-Rolipram	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.

Secondary Outcome Measures

Name	Time	Method
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)	Participants rated level of depression using Montgomery-Åsberg Depression Rating Scale (MADRS). MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Each item yields a score of 0 to 6 with overall score ranging from 0 to 60. Higher MADRS score indicates more severe depression. Scores were measured at two visits, pre-Ketamine administration and a second visit post-Ketamine administration.
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)	Participants rated level of depression using the Hamilton Depression (HAM-D) Rating Scale. The HAM-D is a clinician-administered depression assessment scale which contains 17 items pertaining to symptoms of depression experienced over the past week. Eight items are rated 0-4 and nine items are rated 0-2 for a minimum score of zero and a maximum score of 50. Higher value indicates worsening depression. Scores were measured at two visits, prior to PET scan pre-Ketamine and a second visit post-Ketamine administration.