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Trial record 4 of 490 for:    ESCITALOPRAM AND Antagonists

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01778686
Recruitment Status : Completed
First Posted : January 29, 2013
Last Update Posted : October 30, 2015
Information provided by (Responsible Party):
Gitte Moos Knudsen, Rigshospitalet, Denmark

Brief Summary:

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine

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 Name: Amino acid drink without tryptophan

Primary Outcome Measures :
  1. 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.

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01778686

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Neurobiology Research Unit, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Gitte Moos Knudsen

Additional Information:
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Responsible Party: Gitte Moos Knudsen, Professor, DMSc, Rigshospitalet, Denmark Identifier: NCT01778686     History of Changes
Other Study ID Numbers: 2012-002056-16
First Posted: January 29, 2013    Key Record Dates
Last Update Posted: October 30, 2015
Last Verified: October 2015
Keywords provided by Gitte Moos Knudsen, Rigshospitalet, Denmark:
Positron Emission Tomography
Additional relevant MeSH terms:
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Muscarinic Antagonists
Cholinergic Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Autonomic Agents
Peripheral Nervous System Agents
Cholinergic Agents
Adrenergic Agents
Antihypertensive Agents
Vasodilator Agents