DepressionPhase 1NCT05522673
[11C]-(R)-Rolipram to Measure cAMP Signaling Before and After Ketamine
A Phase 1 study testing 11(R)-rolipram in people with Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Depression
- What is being tested?
- 11(R)-rolipram
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2023to 30 Jan 2024
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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 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 substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use affects the function of daily life.
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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....
Read the 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.
- Conditions
- Depression
- Being tested
- 11(R)-rolipram
- Keywords
- PET Imaging, Inflammation, Ketamine, Depression
- Medical subject headings
- Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
11(R)-rolipramDrug
Injected IV followed by PET scanning
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: 11(R)-rolipram |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 minutes after injection of 11C-R-Rolipram
Secondary outcomes (2)
Measure of Level of Depression Using Montgomery-Åsberg Depression Rating Scale (MADRS)
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.
Measured: 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
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.
Measured: Within two weeks of start of study (Pre) and within 7 days of Ketamine infusion (Post)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2022
- Study start8 Feb 2023
- Primary completion8 Feb 2023
- Study completion30 Jan 2024
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert B Innis, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05522673
- Sponsor's protocol ID
- 10000824
- Other IDs
- 000824-M
- Status last verified
- Jan 2024
- First submitted
- 30 Aug 2022
- Last updated
- 5 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- [11C]-(R)-Rolipram to Measure cAMP Signaling Before and After Ketamine
- ClinicalTrials.gov ID
- NCT05522673
- Acronym / sponsor ID
- 10000824
- Conditions
- Depression
- Keywords
- PET Imaging, Inflammation, Ketamine, Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 8 Feb 2023 (actual)
- Primary completion
- 8 Feb 2023 (actual)
- Study completion
- 30 Jan 2024 (actual)
- First posted
- 31 Aug 2022 (actual)
- Results
- Posted 5 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects with major depression disorder (MDD) | Other | Drug: 11(R)-rolipramParticipants 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (14 listed)
- 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 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 substance use disorder or alcohol use disorder. However, alcohol or cannabis use by themselves are not exclusion criteria, unless that use affects the function of daily life.
- Participants who, in the investigator s judgment, pose a current serious suicidal or homicidal risk.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 11(R)-rolipramInjected IV followed by PET scanning | Drug | Subjects with major depression disorder (MDD) |
Primary outcome
Whole Brain Total Distribution Volume (VT)
Time frame: 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.
2 secondary outcomes
Measure of Level of Depression Using Montgomery-Åsberg Depression Rating Scale (MADRS)
Time frame: 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
Time frame: Within two weeks of start of study (Pre) and within 7 days of Ketamine infusion (Post)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert B Innis, M.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 11(R)-rolipram in people with Depression, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole Brain Total Distribution Volume (VT) (time frame: 90 minutes after injection of 11C-R-Rolipram). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.