Effects of Oxytocin Administered Orally Using a Medicated Lollipop on Peripheral Concentrations and Attention

Study Overview
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Brief Summary
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The study will investigate whether oxytocin (24IU) administered orally using medicated lollipops results in increased peripheral oxytocin concentrations and can modulate social attention in an anti-saccade paradigm in the same way as when it is administered by intranasal or lingual routes.

Detailed Description
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In a triple-blind, placebo-controlled experiment, 72 adult male subjects will be randomly allocated to either receive oral oxytocin (24IU - medicated lollipop - n = 36) or placebo (lollipop without oxytocin - n = 36). After treatment allocation, all subjects will first fill out a set of questionnaires as a control for potential confounders, including Beck Depression Inventory-II (BDI), State-Trait Anxiety Inventory (STAI), Autism Spectrum Quotient (ASQ), the Second Version of Social Responsiveness Scale (SRS-2), Childhood Trauma Questionnaire (CTQ), Toronto Alexithymia Scale (TAS), and Positive Affect Negative Affect Scale (PANAS). Immediately before and 30 minutes after oral treatment administration, subjects will have 5 ml blood samples taken for assay of oxytocin concentrations. Subjects will sit quietly and relax in between blood samples. After the second blood sample, subjects will be positioned sitting in front of an eye-tracking machine and briefly practicing the anti-saccade task. Subjects will then perform the full anti-saccade eye-tracking task, which includes both social (emotional faces - angry, fear, happy, sad, and neutral) and non-social (oval shapes or houses) stimuli (similar to previous studies using intranasal -see NCT03486925 and NCT04493515). After the task, subjects will be asked to guess which treatment they received, and their ability to do so analyzed using chi-squared. Treatment effects on primary (anti-saccade and pro-saccade errors and response latencies) outcomes will be analyzed using ANOVAs. In a secondary analysis, associations between primary outcome measures and basal and altered oxytocin concentrations will be analyzed using Pearson or Spearman correlations. Additionally, a comparison between the effects of oxytocin administered intranasally, lingually (using previously published data), and orally (medicated lollipop) on outcome measures will be analyzed using ANOVA.

Official Title
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Efficacy of Administering Oxytocin Orally Using a Medicated Lollipop Approach on Peripheral Concentrations and Attention: Comparisons With Intranasal and Lingual Spray Administration

Conditions
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Healthy

Intervention / Treatment
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* Drug: oral lollipop with oxytocin (24IU)
* Drug: oral lollipop with placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects without any past or present psychiatric or neurological disorders Exclusion Criteria: History of brain injury Head trauma Substance abuse Medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled triple-blind between-subject design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral oxytocin<br>oral lollipop with oxytocin (24IU) | Drug: oral lollipop with oxytocin (24IU)<br>* Immediately before drug administration, a blood sample (5ml) is collected. For drug administration, participants will be instructed to suck the lollipop medicated with 24IU oxytocin for 3 minutes and then to sit relaxed in a quiet room for 30 minutes prior to taking another blood sample (5ml). Participants then start the anti-saccade attention task 45 minutes after drug administration.<br>* Other names: oral oxytocin;|
| Placebo Comparator: oral lollipop with placebo<br>Placebo orally (identical ingredients, except the active agent) | Drug: oral lollipop with placebo<br>* Immediately before drug administration, a blood sample (5ml) is collected. For placebo administration, participants will be instructed to suck the placebo lollipop for 3 minutes and then to sit relaxed in a quiet room for 30 minutes prior to taking another blood sample (5ml). Participants then start the anti-saccade attention task 45 minutes after placebo administration.<br>* Other names: oral placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral oxytocin effect on error rates of saccade/anti-saccade to social (faces) and non-social (shape) cues between the oxytocin and placebo groups. | A mixed ANOVA to compare differences in error rates in saccade/anti-saccade to different conditions (social/non-social) between two treatment groups. | 45minutes   100 minutes after oral lollipop | 
| Oral oxytocin effect on latencies (in milliseconds) of saccade/anti-saccade to social (faces) and non-social (shape) cues between the oxytocin and placebo groups. | A mixed ANOVA to compare differences of latencies (in milliseconds) in saccade/anti-saccade to different conditions (social/non-social) between two treatment groups. | 45minutes   100 minutes after oral lollipop | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma oxytocin concentrations (pg/ml) before (basal) and 30 minutes after oral oxytocin or placebo administration. | Differences in plasma oxytocin concentrations between the two treatment groups before and after the oral administration will be analyzed using mixed ANOVA, with time point and treatment group as independent variables. | 30 minutes after oral lollipop | 
| Change of Mood as assessed by the Positive Affect Negative Affect Scale (PANAS) before and after the experiment in two treatment groups. | The Positive Affect Negative Affect Scale (PANAS) measures both positive and negative emotions in a person. The Positive Affect score range from 10-50, with higher scores representing higher levels of positive affect. The Negative Affect scores range from 10-50, with lower scores representing lower levels of negative affect. The differences in PANAS scores in pre-/post-experiment between treatment groups will be analyzed using mixed ANOVA. | 45minutes   100 minutes after oral lollipop | 
| Change of state anxiety as assessed by the State-Trait Anxiety Inventory (STAI) before and after the experiment in two treatment groups. | The State-Trait Anxiety Inventory (STAI) is a commonly used measure of the trait (TAI) and state (SAI) anxiety. Each type of anxiety has its own scale of 20 different questions that are scored, and scores range from 20-80, with higher scores indicating greater anxiety. Differences in state anxiety (SAI) scores in pre-/post-experiment between treatment groups will be analyzed using mixed ANOVA. | 45minutes   100 minutes after oral lollipop | 
| Associations between plasma oxytocin concentration changes and task performance (error rates, latencies), mood (PANAS), and state anxiety (SAI). | Pearson or Spearman correlation analysis between plasma oxytocin concentration changes (%) and error rates (%). Pearson or Spearman correlation analysis between plasma oxytocin concentration changes (%) and latencies in milliseconds. Pearson or Spearman correlation analysis between plasma oxytocin concentration changes (%) and post-task PANAS scores. Pearson or Spearman correlation analysis between plasma oxytocin concentration changes (%) and post-task SAI scores. | 45minutes   100 minutes after oral lollipop | 
| Comparison between the effects of oxytocin administered intranasally, lingually, and orally on anti-saccade errors (%) by mixed ANOVA. | Comparisons between anti-saccade errors in the current oral oxytocin administration experiment and those in previous ones using intranasal and lingual oxytocin administration (NCT03486925 and NCT04493515) will be made using mixed ANOVAs, with route (intranasal/lingual/oral) and treatment (oxytocin/placebo) as between-subject factors, condition (social/non-social) as within-subject factor. | 45minutes   100 minutes after oral lollipop | 
| Comparison between the effects of oxytocin administered intranasally, lingually, and orally on latencies in milliseconds by mixed ANOVA. | Comparisons between anti-saccade latencies (in milliseconds) in the current oral oxytocin administration experiment and those in previous ones using intranasal and lingual oxytocin administration (NCT03486925 and NCT04493515) will be made using mixed ANOVAs, with route (intranasal/lingual/oral) and treatment (oxytocin/placebo) as between-subject factors, condition (social/non-social) as within-subject factor. | 45minutes   100 minutes after oral lollipop | 
| Comparison between the effects of oxytocin administered intranasally, lingually, and orally in state anxiety (measured by the State-Trait Anxiety Inventory) changes by mixed ANOVA. | The State-Trait Anxiety Inventory (STAI) measures both trait (TAI) and state (SAI) anxiety. Each type of anxiety has its own scale of 20 different questions that are scored, and scores range from 20-80, with higher scores indicating greater anxiety. Comparisons between changes of state anxiety (SAI) in the current oral oxytocin administration experiment and those in previous ones using intranasal and lingual oxytocin administration (NCT03486925 and NCT04493515) will be made using mixed ANOVAs, with route (intranasal/lingual/oral) and treatment (oxytocin/placebo) as between-subject factors, condition (social/non-social) as within-subject factor. changes = (post-task SAI scores - pre-task SAI scores). | 45minutes   100 minutes after oral lollipop | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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social salience, oral oxytocin, antisaccade paradigm, attention