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NCT Number: NCT01778686

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

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.

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Key information

Conditions

Healthy

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Citalopram and Pindolol

Drug

Citalopram: selective serotonin reuptake inhibitor

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

Other names: Seropram, Hexapindol®

Placebo

Other

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 depletion

Dietary Supplement

Other names: Amino acid drink without tryptophan

Primary outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

Gitte Moos Knudsen

Other

Registry information

Important dates

Study start
2013
Primary completion
2013
Study completion
2013
First posted
Jan 29, 2013
Registry last updated
Feb 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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