HealthyNCT01778686
Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
A study testing Citalopram and Pindolol and Acute tryptophan depletion in people with Healthy, run by Gitte Moos Knudsen at 1 site in Denmark.
Trial summary
The purpose of this project was to introduce the recently developed positron emission tomography (PET) tracer [11C]Cimbi-36 for use in clinical studies and to investigate the ability of the tracer to quantify the 5-HT2A receptor in the human brain. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Citalopram and Pindolol and Acute tryptophan depletion
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2013to Nov 2013
- Phase
- Interventional
- 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 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Generally healthy
Who cannot join
- primary psychiatric disorder
- current or previous neurological disease, severe somatic disease or taking medications that can influence the results.
- non-fluent in danish or severe visual or hearing impairment
- current or previous learning difficulties
- pregnancy or lactating
- contraindications for magnetic resonance scanning
Show all 9Show fewer
- alcohol or drug abuse
- allergy to any of the used medications
- participation in studies with radioactivity (>10 mSv) within the last year or significant occupational exposure to radioactivity.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this project was to introduce the recently developed positron emission tomography (PET) tracer [11C]Cimbi-36 for use in clinical studies and to investigate the ability of the tracer to quantify the 5-HT2A receptor in the human brain. As a receptor agonist, [11C]Cimbi-36 binding will provide a more functional picture of 5-HT2A receptors, while this binding is thought to be correlated to brain serotonin levels. Both measurement of signaling through the 5-HT2A receptor and measurement of serotonin levels in vivo would have great scientific relevance for significant diseases such as depression and schizophrenia.
Read the detailed description
The serotonin 2A (5-HT2A) receptor is the most abundant excitatory serotonin (5-HT, 5-hydroxytryptamine) receptor in the human brain, and multiple positron emission tomography (PET) studies have investigated the 5-HT2A receptors in the human brain using antagonist radioligands. However, the currently available antagonist PET radioligands bind the total pool of 5-HT2A receptor receptors whereas a 5-HT2A receptor agonist binds the high-affinity subgroup of the receptors which are also G-protein coupled, and thus hypothesized to be the functional relevant population of receptors. At the Center for Integrated Molecular Brain Imaging (CIMBI), a novel agonist PET radioligands for brain imaging of 5-HT2A receptors was recently validated in animals (Ettrup et al. 2011, EJNMMI). In the human brain, [11C]Cimbi-36 was validated as a selective 5-HT2A receptor agonist PET radioligand through a blocking study with the 5-HT2A receptor antagonist pharmaceutical ketanserin. In this validation study, the biodistribution and kinetic modelling of [11C]Cimbi-36 binding in the human brain was also validated. With these studies, investigators will test the most promising of these, [11C]Cimbi-36, in clinical trials, where it will provide a novel method for detecting dysfunction in the 5-HT system. The specific aim of this clinical trial is:
- To examine the effect of acute alterations in 5-HT levels on cerebral [11C]Cimbi-36 binding in healthy volunteers who will be PET-scanned at baseline and after pharmacological or dietary interventions that either increase or decrease cerebral 5-HT levels.
It is hypothesized that this novel agonist radioligand will provide both a more physiological relevant measure of the 5-HT2A receptors and also reflect levels of cerebral 5-HT in humans, more specifically:
BP will decrease after pindolol and selective serotonin reuptake inhibitor (SSRI) treatment and increase after acute tryptophan depletion (ATD). Placebo will leave binding potential (BP) unchanged.
- Conditions
- Healthy
- Being tested
- Citalopram and Pindolol, Placebo, Acute tryptophan depletion
- Keywords
- Positron Emission Tomography, Serotonin, 5-HT2A, Radioligand
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Citalopram and PindololDrug
Also called Seropram, Hexapindol®
Citalopram: selective serotonin reuptake inhibitor
Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist
PlaceboOther
On the second PET scanning day, subjects received a protein drink as well as a 50 ml saline infusion over 1 hour starting 30 min before PET scanning.
Acute tryptophan depletionDietary supplement
Also called Amino acid drink without tryptophan
| Study group | Role | What they receive |
|---|---|---|
| Citalopram and Pindolol | Experimental | Citalopram intravenous infusion starting 30 min before scanning, 40 mg/h for 1 hour.
Pindolol peroral administration starting 3 days before scanning:
Day 1: 2.5 mg 3 times daily, day 2: 5 mg 3 times daily, day 3: 7.5 mg 3 times daily, Day 4 (scan day) 7.5 mg morning and noon. Receives: Drug: Citalopram and Pindolol |
| Placebo | Placebo comparator | Placebo for pindolol: sugar tablets that resembles pindolol
Placebo for ATD: amino acid drink balanced formula (containing tryptophan)
Placebo for Seropram: NaCl infusion Receives: Other: Placebo |
| Acute tryptophan depletion | Experimental | Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning. Receives: Dietary Supplement: Acute tryptophan depletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm
Cerebral Cimbi-36 receptor binding is measured with PET scanning for 2 hours, at baseline and after intervention. The resultant time-activity curves for brain tissue are used together with time-activity curves obtained with blood samples and kinetic modelling to yield unitless values of BPND at baseline and after intervention, respectively. As outcome, the mean percent difference from baseline to intervention in each arm is measured.
Measured: 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionNov 2013
- Study completionNov 2013
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gitte Moos Knudsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gitte Moos Knudsen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Gitte M Knudsen, DMSc, Principal investigator, Neurobiology Research Unit, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01778686
- Sponsor's protocol ID
- 2012-002056-16
- Status last verified
- Jan 2025
- First submitted
- 11 Jan 2013
- Last updated
- 20 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers. Eur J Nucl Med Mol Imaging. 2011 Apr;38(4):681-93. doi: 10.1007/s00259-010-1686-8. Epub 2010 Dec 21.
PubMed 21174090
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
- ClinicalTrials.gov ID
- NCT01778686
- Acronym / sponsor ID
- 2012-002056-16
- Conditions
- Healthy
- Keywords
- Positron Emission Tomography, Serotonin, 5-HT2A, Radioligand
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Gitte Moos KnudsenUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 29 Jan 2013 (estimated)
- Results
- Posted 9 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this project was to introduce the recently developed positron emission tomography (PET) tracer [11C]Cimbi-36 for use in clinical studies and to investigate the ability of the tracer to quantify the 5-HT2A receptor in the human brain. As a receptor agonist, [11C]Cimbi-36 binding will provide a more functional picture of 5-HT2A receptors, while this binding is thought to be correlated to brain serotonin levels. Both measurement of signaling through the 5-HT2A receptor and measurement of serotonin levels in vivo would have great scientific relevance for significant diseases such as depression and schizophrenia.
Detailed description
The serotonin 2A (5-HT2A) receptor is the most abundant excitatory serotonin (5-HT, 5-hydroxytryptamine) receptor in the human brain, and multiple positron emission tomography (PET) studies have investigated the 5-HT2A receptors in the human brain using antagonist radioligands. However, the currently available antagonist PET radioligands bind the total pool of 5-HT2A receptor receptors whereas a 5-HT2A receptor agonist binds the high-affinity subgroup of the receptors which are also G-protein coupled, and thus hypothesized to be the functional relevant population of receptors. At the Center for Integrated Molecular Brain Imaging (CIMBI), a novel agonist PET radioligands for brain imaging of 5-HT2A receptors was recently validated in animals (Ettrup et al. 2011, EJNMMI). In the human brain, [11C]Cimbi-36 was validated as a selective 5-HT2A receptor agonist PET radioligand through a blocking study with the 5-HT2A receptor antagonist pharmaceutical ketanserin. In this validation study, the biodistribution and kinetic modelling of [11C]Cimbi-36 binding in the human brain was also validated. With these studies, investigators will test the most promising of these, [11C]Cimbi-36, in clinical trials, where it will provide a novel method for detecting dysfunction in the 5-HT system. The specific aim of this clinical trial is:
- To examine the effect of acute alterations in 5-HT levels on cerebral [11C]Cimbi-36 binding in healthy volunteers who will be PET-scanned at baseline and after pharmacological or dietary interventions that either increase or decrease cerebral 5-HT levels.
It is hypothesized that this novel agonist radioligand will provide both a more physiological relevant measure of the 5-HT2A receptors and also reflect levels of cerebral 5-HT in humans, more specifically:
BP will decrease after pindolol and selective serotonin reuptake inhibitor (SSRI) treatment and increase after acute tryptophan depletion (ATD). Placebo will leave binding potential (BP) unchanged.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Citalopram and Pindolol | Experimental | Drug: Citalopram and PindololCitalopram intravenous infusion starting 30 min before scanning, 40 mg/h for 1 hour. Pindolol peroral administration starting 3 days before scanning: Day 1: 2.5 mg 3 times daily, day 2: 5 mg 3 times daily, day 3: 7.5 mg 3 times daily, Day 4 (scan day) 7.5 mg morning and noon. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo for pindolol: sugar tablets that resembles pindolol Placebo for ATD: amino acid drink balanced formula (containing tryptophan) Placebo for Seropram: NaCl infusion |
| Acute tryptophan depletion | Experimental | Dietary Supplement: Acute tryptophan depletionAmino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age > 18 years
- Generally healthy
Key exclusion criteria (9 listed)
- primary psychiatric disorder
- current or previous neurological disease, severe somatic disease or taking medications that can influence the results.
- non-fluent in danish or severe visual or hearing impairment
- current or previous learning difficulties
- pregnancy or lactating
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 |
|---|---|---|
| Citalopram and PindololAlso: Seropram, Hexapindol®Citalopram: selective serotonin reuptake inhibitor Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist | Drug | Citalopram and Pindolol |
| PlaceboOn the second PET scanning day, subjects received a protein drink as well as a 50 ml saline infusion over 1 hour starting 30 min before PET scanning. | Other | Placebo |
| Acute tryptophan depletionAlso: Amino acid drink without tryptophan | Dietary supplement | Acute tryptophan depletion |
Primary outcome
Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm
Time frame: 2 hours
Cerebral Cimbi-36 receptor binding is measured with PET scanning for 2 hours, at baseline and after intervention. The resultant time-activity curves for brain tissue are used together with time-activity curves obtained with blood samples and kinetic modelling to yield unitless values of BPND at baseline and after intervention, respectively. As outcome, the mean percent difference from baseline to intervention in each arm is measured.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21174090Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers. Eur J Nucl Med Mol Imaging. 2011 Apr;38(4):681-93. doi: 10.1007/s00259-010-1686-8. Epub 2010 Dec 21.
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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.
Gitte M Knudsen, DMSc principal investigator
Neurobiology Research Unit, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Citalopram and Pindolol and Acute tryptophan depletion in people with Healthy, run by Gitte Moos Knudsen at 1 site in Denmark.
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 2 inclusion and 9 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: finished, as of the sponsor's last update on 20 Feb 2025. 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 Denmark. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 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?
Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm (time frame: 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01778686, which also lists 1 linked publication.
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 20 Feb 2025.