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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Rigshospitalet, Denmark
Sponsor:
Information provided by (Responsible Party):
Gitte Moos Knudsen, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01778686
First received: January 11, 2013
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

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 Intervention
Healthy
Drug: Citalopram and Pindolol
Dietary Supplement: Acute tryptophan depletion

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 30
Study Start Date: January 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Experimental: Acute tryptophan depletion
Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning.
Dietary Supplement: Acute tryptophan depletion
Amino acid drink without tryptophan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778686

Locations
Denmark
Neurobiology Research Unit, Rigshospitalet Recruiting
Copenhagen, Denmark, 2100
Contact: Gitte M Knudsen, DMSc    +45 35456712    gmk@nru.dk   
Sponsors and Collaborators
Gitte Moos Knudsen
  More Information

Additional Information:
Publications:
Responsible Party: Gitte Moos Knudsen, Professor, DMSc, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01778686     History of Changes
Other Study ID Numbers: 2012-002056-16
Study First Received: January 11, 2013
Last Updated: January 25, 2013
Health Authority: Denmark: Danish Health and Medicines Authority

Keywords provided by Rigshospitalet, Denmark:
Positron Emission Tomography
Serotonin
5-HT2A
Radioligand

Additional relevant MeSH terms:
Citalopram
Serotonin Uptake Inhibitors
Tryptophan
Dexetimide
Pindolol
Serotonin
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 20, 2014