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

NCT01778686 | Completed Results DMC

• 1 other identifier: 2012-002056-16
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Positron Emission Tomography; Serotonin; 5-HT2A; Radioligand

Outcome Measures

Primary Outcomes (1)

• Percent Change in Neocortical [11C]Cimbi-36 BPND From Baseline to Intervention in Each Arm

  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.

  2 hours

Study Arms (3)

Citalopram and Pindolol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Acute tryptophan depletion

EXPERIMENTAL

Amino acid drink without tryptophan. Ingested 4-5 hours prior to PET scanning.

Dietary Supplement: Acute tryptophan depletion

Interventions

Citalopram and Pindolol DRUG

Citalopram: selective serotonin reuptake inhibitor Pindolol: non-selective beta blocker and 5-HT1A receptor antagonist

Also known as: Seropram, Hexapindol®

Citalopram and Pindolol

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.

Placebo

Acute tryptophan depletion DIETARY_SUPPLEMENT

Also known as: Amino acid drink without tryptophan

Acute tryptophan depletion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Generally healthy

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gitte Moos Knudsen: lead

Study Sites (1)

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (1)

• 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.

  PMID: 21174090 BACKGROUND

MeSH Terms

Interventions

Citalopram; Pindolol; Tryptophan

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Results Point of Contact

• Title: Gitte Moos Knudsen
• Organization: Rigshospitalet and University of Copenhagen

gmk@nru.dk

+4535456720

Study Officials

• Gitte M Knudsen, DMSc

  Neurobiology Research Unit, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, DMSc

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: January 29, 2013
• Study Start: January 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: February 20, 2025
• Results First Posted: October 9, 2024

Record last verified: 2025-01

Locations

DK (1)