Effects of Oxytocin on Cognitive and Reactive Fear

NCT ID: NCT04292444

Last Updated: 2020-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-12-13

Study Completion Date

2021-05-31

Brief Summary

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The study examines the (sub)regional specificity of anxiolytic oxytocin (OXT) effects on emotional face processing and reactive and cognitive fear. Preliminary data indicate that the Receptor for Advanced Glycation End Products (RAGE) may regulate oxytocin transport into the brain. Thus, the study aims to replicate previous observations of oxytocin effects on the processing of fearful faces in the centro-medial amygdala and to assess whether a RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA), that has been shown to alter transcriptional activity, modulates anxiolytic OXT effects.

Detailed Description

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So far, no study examined selective oxytocin (OXT) effects on reactive (midbrain periaqueductal gray (PAG), central amygdala (CeA), hypothalamus, and the midcingulate cortex (MCC)) and cognitive fear (ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), hippocampus, and basolateral amygdala) and the reward system (striatum) with high spatial resolution. Previous studies showed that 7T functional magnetic resonance imaging (fMRI) results in a higher spatial resolution and specificity than 3T MRI in these brain regions and would thus allow for a more detailed characterization of the neural effects.

To disentangle (sub)region-specific effects of OXT on task-related activations of the cingulate structures, the amygdala, the striatum, PAG and VMPFC, the investigators plan to acquire ultra-high field 7T fMRI data from healthy male participants while they perform (i) an emotional face matching task and (ii) a flight initiation distance (FID) task involving fast- or slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. Furthermore, participants will be pre-stratified depending on RAGE polymorphisms to elucidate possible RAGE-related differential OXT effects.

Conditions

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Oxytocin

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

The study is designed as a double-blind, within-subject, placebo-controlled, non-clinical trial and will involve healthy male participants (n = 60), who will be scanned twice in a randomized order after a single dose of intranasal OXT (24 IU) or placebo. Furthermore participants will be pre-stratified based on a RAGE polymorphism (-374 T/A: rs1800624; n = 30 with TT alleles and n = 30 with TA/AA alleles).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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RAGE polymorphism (TT)

30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TT) will be selected and scanned twice.

Group Type EXPERIMENTAL

Oxytocin nasal spray

Intervention Type DRUG

Intranasal administration of 24 International Units oxytocin 30 minutes before the start of the tasks.

Placebo

Intervention Type DRUG

The placebo nasal sprays contain identical ingredients except for the peptide itself (30 minutes before the start of the tasks).

RAGE polymorphism (TA/AA)

30 participants with the RAGE polymorphism (-374 T/A: rs1800624; TA/AA) will be selected and scanned twice.

Group Type EXPERIMENTAL

Oxytocin nasal spray

Intervention Type DRUG

Intranasal administration of 24 International Units oxytocin 30 minutes before the start of the tasks.

Placebo

Intervention Type DRUG

The placebo nasal sprays contain identical ingredients except for the peptide itself (30 minutes before the start of the tasks).

Interventions

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Oxytocin nasal spray

Intranasal administration of 24 International Units oxytocin 30 minutes before the start of the tasks.

Intervention Type DRUG

Placebo

The placebo nasal sprays contain identical ingredients except for the peptide itself (30 minutes before the start of the tasks).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA)
* healthy male volunteers
* right handed

Exclusion Criteria

* current psychiatric illness
* current psychiatric medication or psychotherapy
* MRI contraindication (e.g. metal in body, claustrophobia)
Minimum Eligible Age

18 Years

Maximum Eligible Age

40 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Bonn

OTHER

Sponsor Role lead

Responsible Party

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Rene Hurlemann

Professor for Psychiatry

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rene Hurlemann, MSc, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oldenburg

Locations

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Department of Psychiatry and Medical Psychology

Bonn, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Dirk Scheele, PhD

Role: CONTACT

+49 (0)228 287 ext. 11151

Marie J Coenjaerts, MSc

Role: CONTACT

+49 (0)228 287 ext. 19704

Facility Contacts

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Dirk Scheele, PhD

Role: primary

References

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Hahn A, Kranz GS, Seidel EM, Sladky R, Kraus C, Kublbock M, Pfabigan DM, Hummer A, Grahl A, Ganger S, Windischberger C, Lamm C, Lanzenberger R. Comparing neural response to painful electrical stimulation with functional MRI at 3 and 7 T. Neuroimage. 2013 Nov 15;82:336-43. doi: 10.1016/j.neuroimage.2013.06.010. Epub 2013 Jun 12.

Reference Type BACKGROUND
PMID: 23769917 (View on PubMed)

Hudson BI, Stickland MH, Futers TS, Grant PJ. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy. Diabetes. 2001 Jun;50(6):1505-11. doi: 10.2337/diabetes.50.6.1505.

Reference Type BACKGROUND
PMID: 11375354 (View on PubMed)

Qi S, Hassabis D, Sun J, Guo F, Daw N, Mobbs D. How cognitive and reactive fear circuits optimize escape decisions in humans. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3186-3191. doi: 10.1073/pnas.1712314115. Epub 2018 Mar 5.

Reference Type BACKGROUND
PMID: 29507207 (View on PubMed)

Yamamoto Y, Liang M, Munesue S, Deguchi K, Harashima A, Furuhara K, Yuhi T, Zhong J, Akther S, Goto H, Eguchi Y, Kitao Y, Hori O, Shiraishi Y, Ozaki N, Shimizu Y, Kamide T, Yoshikawa A, Hayashi Y, Nakada M, Lopatina O, Gerasimenko M, Komleva Y, Malinovskaya N, Salmina AB, Asano M, Nishimori K, Shoelson SE, Yamamoto H, Higashida H. Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice. Commun Biol. 2019 Feb 25;2:76. doi: 10.1038/s42003-019-0325-6. eCollection 2019.

Reference Type BACKGROUND
PMID: 30820471 (View on PubMed)

Hariri AR, Tessitore A, Mattay VS, Fera F, Weinberger DR. The amygdala response to emotional stimuli: a comparison of faces and scenes. Neuroimage. 2002 Sep;17(1):317-23. doi: 10.1006/nimg.2002.1179.

Reference Type BACKGROUND
PMID: 12482086 (View on PubMed)

Related Links

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http://renehurlemann.squarespace.com/welcome/

Neuromodulation of Emotion (NEMO) Research Group

Other Identifiers

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RAGE

Identifier Type: -

Identifier Source: org_study_id

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