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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

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ClinicalTrials.gov Identifier: NCT01778686
Recruitment Status : Completed
First Posted : January 29, 2013
Last Update Posted : October 30, 2015
Sponsor:
Information provided by (Responsible Party):
Gitte Moos Knudsen, Rigshospitalet, Denmark

Tracking Information
First Submitted Date  ICMJE January 11, 2013
First Posted Date  ICMJE January 29, 2013
Last Update Posted Date October 30, 2015
Study Start Date  ICMJE January 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01778686 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
Official Title  ICMJE Evaluation of [11C]Cimbi-36 as an Agonist PET Radioligand for Imaging of 5-HT2A Receptors
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Citalopram and Pindolol

    Citalopram: selective serotonin reuptake inhibitor

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

    Other Names:
    • Seropram
    • Hexapindol®
  • 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.
  • Dietary Supplement: Acute tryptophan depletion
    Other Name: Amino acid drink without tryptophan
Study Arms  ICMJE
  • 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.

    Intervention: Drug: Citalopram and Pindolol
  • 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

    Intervention: Other: Placebo
  • Experimental: Acute tryptophan depletion
    Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning.
    Intervention: Dietary Supplement: Acute tryptophan depletion
Publications * Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM. Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers. Eur J Nucl Med Mol Imaging. 2011 Apr;38(4):681-93. doi: 10.1007/s00259-010-1686-8. Epub 2010 Dec 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 5, 2014)
24
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2013)
30
Actual Study Completion Date  ICMJE November 2013
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01778686
Other Study ID Numbers  ICMJE 2012-002056-16
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gitte Moos Knudsen, Rigshospitalet, Denmark
Study Sponsor  ICMJE Gitte Moos Knudsen
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Rigshospitalet, Denmark
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP