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Report for Clinical Trial NCT04292444

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Disentangling Effects of Oxytocin on Cognitive and Reactive Fear and the Moderating Role of the Receptor for Advanced Glycation End-products

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 (Yamamoto et al., 2019). 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 (Hudson et al., 2001), modulates anxiolytic OXT effects.

NCT04292444 Oxytocin

2 Interventions

Name: Oxytocin nasal spray

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

Type: Drug

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

Name: Placebo

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

Type: Drug

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


Primary Outcomes

Description: 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.

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

Time: 30 min after nasal spray administration

Description: 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.

Measure: Neural responses in the flight initiation distance (FID) task

Time: 45 min after nasal spray administration

Description: 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.

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

Time: 45 min after nasal spray administration

Secondary Outcomes

Description: Blood samples will be collected before and after the nasal spray administration to assess changes in oxytocin concentrations. Oxytocin concentrations will be analyzed using mixed ANOVAs in SPSS with time (pre vs. post) and treatment (oxytocin vs. placebo) as within-subject factors and RAGE polymorphism (TT vs. TA/AA) as between-subject factor.

Measure: Oxytocin concentration in blood plasma

Time: Before nasal spray administration and 75 min after nasal spray administration

Description: Blood samples will be collected before the nasal spray administration to assess the RAGE (extracellular domain) concentration in blood plasma. RAGE concentrations will be compared between RAGE polymorphisms (TT vs. TA/AA) with independent t-tests. Furthermore, the investigators plan to examine if the RAGE concentration moderates the effects of oxytocin on primary and secondary outcomes.

Measure: RAGE (extracellular domain) concentration in blood plasma

Time: Before nasal spray administration

Purpose: Basic Science

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 rs1800624

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 (Hudson et al., 2001), modulates anxiolytic OXT effects.

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.

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.

Furthermore, the investigators plan to examine if the RAGE concentration moderates the effects of oxytocin on primary and secondary outcomes.. 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) 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.



HPO Nodes