Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors

January 30, 2025 updated by: Gitte Moos Knudsen
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

24

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Neurobiology Research Unit, Rigshospitalet

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age > 18 years
  • Generally healthy

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Citalopram and Pindolol

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.
Drug: Citalopram and Pindolol

Citalopram: selective serotonin reuptake inhibitor

Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist

Other Names:
  • Seropram
  • Hexapindol®
Placebo Comparator: Placebo

Placebo for pindolol: sugar tablets that resembles pindolol

Placebo for ATD: amino acid drink balanced formula (containing tryptophan)

Placebo for Seropram: NaCl infusion
Other: Placebo
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.
Experimental: Acute tryptophan depletion
Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning.
Dietary supplement: Acute tryptophan depletion
Other Names:
  • Amino acid drink without tryptophan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gitte Moos Knudsen

Investigators

  • Principal Investigator: Gitte M Knudsen, DMSc, Neurobiology Research Unit, Rigshospitalet

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

January 11, 2013

First Submitted That Met QC Criteria

January 25, 2013

First Posted (Estimated)

January 29, 2013

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 30, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2012-002056-16

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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