Effects of Oxytocin on Cognitive and Reactive Fear

NCT04292444 | Unknown Phase 1

• 1 other identifier: RAGE
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oxytocin

Keywords

fMRI; receptor for advanced glycation end-products (RAGE); fear; 7T MRI

Outcome Measures

Primary Outcomes (3)

• Neural substrates of emotion processing, measured via blood-oxygen-level dependent (BOLD) signal in the amygdala and striatum

  Functional magnetic resonance imaging will be performed to measure the BOLD signal in response to emotional face stimuli. The investigators specifically plan to investigate neural responses to emotional faces in amygdala and striatal subregions. The BOLD signal in response to fearful faces relative to neutral faces and happy faces relative to neutral will be compared between the oxytocin and placebo sessions. To examine effects of the Receptor for Advanced Glycation End Products (RAGE), analyses of variance (ANOVAs) with the between subjects factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the second level. For analyses of fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging. The family-wise error rate will be used to correct p-values for multiple comparisons and p \< .05 will be considered significant.

  30 minutes after nasal spray administration

• Neural responses in the flight initiation distance (FID) task

  Functional magnetic resonance imaging will be performed to measure the blood-oxygen-level dependent (BOLD) signal in a flight initiation distance (FID) task, involving fast-, medium- and slow-attacking virtual predators that elicit distinct activations in the reactive and cognitive fear circuits. BOLD signals to different predator velocities will be analyzed. Analyses will focus on regions-of-interest associated with the processing of cognitive fear (vmPFC, PCC, hippocampus, and basolateral amygdala) and reactive fear (midbrain PAG, central amygdala, hypothalamus, and the MCC) and the reward system (striatum). To examine effects of the Receptor for Advanced Glycation End Products (RAGE), ANOVAs with the between-subject factor RAGE polymorphism (-374 T/A: rs1800624; TT vs. TA/AA) will be conducted on the 2nd level. For the fMRI data, default procedures of the software SPM12 will be adapted for ultra-high-field imaging.

  45 minutes after nasal spray administration

• Flight distance and difficulty ratings in the flight initiation distance (FID) task

  Behavioral data of the FID task (flight distance and difficulty ratings ) will be analyzed using mixed ANOVAs in the software SPSS with treatment (oxytocin vs. placebo) as within-subject factor and RAGE polymorphism (TT vs. TA/AA) as between-subject factor. Post-hoc t-tests will be Bonferroni-corrected. Behavioral data will be correlated with fMRI data of the FID task.

  45 minutes after nasal spray administration

Secondary Outcomes (2)

• Oxytocin concentration in blood plasma

  10 minutes before nasal spray administration and 75 minutes after nasal spray administration

• Concentration of receptor for advanced glycation endproducts (extracellular domain) in blood plasma

  10 minutes before nasal spray administration

Study Arms (2)

RAGE polymorphism (TT)

EXPERIMENTAL

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

Drug: Oxytocin nasal spray; Drug: Placebo

RAGE polymorphism (TA/AA)

EXPERIMENTAL

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

Drug: Oxytocin nasal spray; Drug: Placebo

Interventions

Oxytocin nasal spray DRUG

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

RAGE polymorphism (TA/AA); RAGE polymorphism (TT)

Placebo 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); RAGE polymorphism (TT)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• current psychiatric illness
• current psychiatric medication or psychotherapy
• MRI contraindication (e.g. metal in body, claustrophobia)

Sponsors & Collaborators

• University Hospital, Bonn: lead

Study Sites (1)

Department of Psychiatry and Medical Psychology

Bonn, 53105, Germany

RECRUITING

Related Publications (5)

• 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.

  PMID: 23769917 BACKGROUND

• 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.

  PMID: 11375354 BACKGROUND

• 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.

  PMID: 29507207 BACKGROUND

• 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.

  PMID: 30820471 BACKGROUND

• 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.

  PMID: 12482086 BACKGROUND

Related Links

• Neuromodulation of Emotion (NEMO) Research Group

Study Officials

• Rene Hurlemann, MSc, MD, PhD

  University of Oldenburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dirk Scheele, PhD

CONTACT

+49 (0)228 287; Dirk.Scheele@ukbonn.de

Marie J Coenjaerts, MSc

CONTACT

+49 (0)228 287; Marie.Coenjaerts@ukbonn.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor for Psychiatry

Model Details: 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).

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 3, 2020
• Study Start: December 13, 2019
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2021
• Last Updated: March 12, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)