Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
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|ClinicalTrials.gov Identifier: NCT01778686|
Recruitment Status : Completed
First Posted : January 29, 2013
Last Update Posted : October 30, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Citalopram and Pindolol Other: Placebo Dietary Supplement: Acute tryptophan depletion||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors|
|Study Start Date :||January 2013|
|Actual Primary Completion Date :||November 2013|
|Actual Study Completion Date :||November 2013|
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
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
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 Name: Amino acid drink without tryptophan
- Cerebral Cimbi-36 receptor binding in terms of binding potential (BP) at (1) baseline (2)acute tryptophan depletion (3) acute SSRI and pindolol (4) placebo [ Time Frame: 2 hours ]Cerebral Cimbi-36 receptor binding is measured with PET scanning for 2 hours. 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 BP.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01778686
|Neurobiology Research Unit, Rigshospitalet|
|Copenhagen, Denmark, 2100|