Effects of Intranasal Administration of a Single Dose of Oxytocin Using a Novel Device in Healthy Adults
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|ClinicalTrials.gov Identifier: NCT01983514|
Recruitment Status : Completed
First Posted : November 14, 2013
Last Update Posted : April 23, 2014
Oxytocin (OT) is a small, naturally occurring peptide currently in clinical use to stimulate lactation in breastfeeding women. The intranasal administration of OT has recently attracted attention as a potential novel treatment in several psychiatric disorders including autism. However, given the anatomy of the nasal cavity, the current design of nasal sprays would be expected to provide an inadequate delivery of medication to the areas of the nasal cavity where direct transport into the brain via the olfactory nerve could potentially occur. OptiNose has developed an intranasal delivery device that provides improved reproducibility of nasal delivery, improved deposition to the upper posterior regions of the nasal cavity where the olfactory nerve innervates the nasal cavity.
The primary objective of this study is to identify any differences between single dose 8 or 24 international units (IU) oxytocin delivered intranasally with the optimised OptiNose device and 1 IU oxytocin administered as slow intravenous infusion in healthy volunteers. This will be measured in terms of brain activity as measured with functional magnetic resonance imaging (fMRI), performance on cognitive tests, and physiological markers.
|Condition or disease||Intervention/treatment||Phase|
|Healthy Male Adults||Drug: 8IU intranasal oxytocin Drug: 24 IU intranasal oxytocin Drug: 1 IU intravenous oxytocin Drug: Placebo||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Intranasal (Optinose Bidirectional Nose-to-brain Device) Versus Intravenous Slow Infusion of Oxytocin - a Randomized, Placebo- Controlled Double-blind, Double-dummy 4-period Cross-over Study in Healthy Adult Volunteers Evaluating Brain Functional Magnetic Resonance Imaging Changes, Cognitive Response, Heart Rate Variability, Plasma Pharmacokinetics and Saliva Concentration After Single-dose Oxytocin 8 or 24 International Units (IU) Intranasally or 1 IU as Slow Intravenous Infusion|
|Study Start Date :||October 2013|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||February 2014|
Active Comparator: 1 international unit (IU) intravenous oxytocin
Using a double-dummy design participants will be administered 1 IU oxytocin (mixed in 200 ml 0.9% sodium chloride) slow infusion with varying infusion rate over 20 minutes and placebo delivered with the OptiNose Breath Powered Bi-Directional liquid device. Subject to pilot data this may be increased to 2 IU oxytocin (mixed in 200 ml 0.9% sodium chloride) and the infusion time/rate may change to best match the pharmacokinetic profile of intranasally administered oxytocin.
Drug: 1 IU intravenous oxytocin
Placebo Comparator: Placebo
Using a double-dummy design participants will be administered Placebo delivered with the OptiNose Breath Powered Bi-Directional liquid device and placebo delivered intravenously (0.9% sodium chloride 200 ml slow infusion for 20 minutes)
Experimental: 8IU intranasal oxytocin
Using a double-dummy design participants will be administered 8IU oxytocin liquid delivered with the OptiNose Breath Powered Bi directional liquid device and IV placebo (0.9% sodium chloride, 200 ml slow infusion for 20 minutes)
Drug: 8IU intranasal oxytocin
Experimental: 24IU intranasal oxytocin
Using a double-dummy design participants will be administered 24IU oxytocin liquid delivered with the OptiNose Breath Powered Bi directional liquid device and IV placebo (0.9% sodium chloride, 200 ml slow infusion for 20 minutes)
Drug: 24 IU intranasal oxytocin
- Aim 1a: Brain activity [ Time Frame: 30 minutes after oxytocin/placebo administration ]Scanning procedures for functional magnetic resonance imaging (fMRI) will include a functional scan during a social cognition task and structural connectivity during rest
- Aim 1b: Performance on a social cognition test [ Time Frame: 45 mins after oxytocin/placebo administration ]Participants will complete a task evaluating emotional expressions (either happy expressions, fear expressions or neutral expressions). These stimuli are identical to those published previously by Leknes et al., (2012).
- Aim 1c: Heart rate variability [ Time Frame: 20 minutes after oxytocin placebo administration ]Electrocardiogram data will be collected to assess heart rate variability, a measure of cardiac autonomic function.
- Aim 1d: Eyetracking [ Time Frame: 20 minutes after oxytocin placebo administration ]An eyetracking device will measure eyegaze and pupillometry.
- Pharmacokinetic (PK) profile of oxytocin [ Time Frame: 5 minutes prior to oxytocin/placebo administration ]Blood will be collected to assess levels of oxytocin present in peripheral blood to measure PK profile of 8 and 24 international units (IU) oxytocin delivered with OptiNose device and of 1 IU oxytocin after slow intravenous (IV) infusion.
- Plasma concentration of cortisol [ Time Frame: 20 minutes before fMRI procedure ]Blood will be drawn at various intervals for the pharmacokinetic analysis of plasma cortisol.
- Oxytocin levels in saliva [ Time Frame: 20 prior to fMRI procedure ]Saliva will be collected for pharmacokinetic analysis of oxytocin and cortisol in saliva.
- Cortisol levels in saliva [ Time Frame: 20 minutes prior to fMRI procedure ]Saliva will be collected for pharmacokinetic analysis of oxytocin and cortisol in saliva.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01983514
|Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research - TOP Study|
|Principal Investigator:||Ole A Andreassen, MD||University of Oslo|