Effects of Intranasal Administration of a Single Dose of Oxytocin Using a Novel Device in Healthy Adults

NCT01983514 | Completed Phase 1

• 1 other identifier: SMR-2727
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Male Adults

Keywords

oxytocin; fMRI; social cognition; heart rate variability; pupillometry; eye tracking

Outcome Measures

Primary Outcomes (4)

• Aim 1a: Brain activity

  Scanning procedures for functional magnetic resonance imaging (fMRI) will include a functional scan during a social cognition task and structural connectivity during rest

  30 minutes after oxytocin/placebo administration

• Aim 1b: Performance on a social cognition test

  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).

  45 mins after oxytocin/placebo administration

• Aim 1c: Heart rate variability

  Electrocardiogram data will be collected to assess heart rate variability, a measure of cardiac autonomic function.

  20 minutes after oxytocin placebo administration

• Aim 1d: Eyetracking

  An eyetracking device will measure eyegaze and pupillometry.

  20 minutes after oxytocin placebo administration

Secondary Outcomes (4)

• Pharmacokinetic (PK) profile of oxytocin

  5 minutes prior to oxytocin/placebo administration

• Plasma concentration of cortisol

  20 minutes before fMRI procedure

• Oxytocin levels in saliva

  20 prior to fMRI procedure

• Cortisol levels in saliva

  20 minutes prior to fMRI procedure

Study Arms (4)

1 international unit (IU) intravenous oxytocin

ACTIVE COMPARATOR

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

PLACEBO COMPARATOR

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)

Drug: Placebo

8IU intranasal oxytocin

EXPERIMENTAL

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

24IU intranasal oxytocin

EXPERIMENTAL

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

Interventions

8IU intranasal oxytocin DRUG

8IU intranasal oxytocin

24 IU intranasal oxytocin DRUG

24IU intranasal oxytocin

1 IU intravenous oxytocin DRUG

1 international unit (IU) intravenous oxytocin

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, male subjects aged 18 to 35 years inclusive.
• Subjects must be in good general health, as determined by the investigator.
• Subject's pre-study physical examination, vital signs and electrocardiogram (ECG) are normal or do not show any clinically significant abnormalities as determined by the investigator. Vital signs must not have any clinically significant deviations outside of the following ranges when measured sitting after 5 minutes rest:
• Heart rate: 40 to 90 beats per minute
• Systolic blood pressure (BP): 90 to 140 mmHg
• Diastolic BP: 50 to 90 mmHg
• Oral temperature: 36.0 to 37.5°C
• Respiratory rate: 12 - 18 breaths per minute
• Body Mass Index (BMI) of 18.5 - 29.9 kg/m2 (both inclusive)
• Subjects must be able to communicate well with the Investigator, to understand and comply with the requirements of the study, and understand and sign the written informed consent
• Provision of written informed consent.

You may not qualify if:

• An ear, nose and throat (ENT) specialist will inspect the noses of all individuals who enter the study.
• Individuals showing major septal deviation or a significantly altered nasal epithelium.
• Participants with evidence of previous nasal disease, surgery, and dependence on inhaled drugs.
• Individuals with current significant nasal congestion due to common colds.
• Subjects with a clinically relevant history of significant hepatic, renal, endocrine, cardiac, nervous, psychiatric, gastrointestinal, pulmonary, haematological or metabolic disorder.
• Subjects with current or history of, any clinically significant disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• Subject is taking any regular prescribed or over-the-counter (OTC) medications including vitamin supplements and herbal remedies. There must be at least 14 days between stopping these products and the first dose of study medication).
• Systemic illness requiring treatment within 2 weeks prior to Study Day 1.
• History of significant drug or alcohol abuse (as per a self-report measure / instrument; World Health Organisation criteria/Alcohol use disorders identification test/Drug use disorders identification test). Subjects with a positive screen for alcohol or drugs of abuse at screening/admission will be excluded from participation in the study.
• Self-reported significant psychiatric conditions.
• Any abnormal laboratory values outside normal range, and which is clinically significant as deemed by investigator.
• Full scale intelligence quotient (IQ) \< 75 (due to the prerequisite ability to complete self report measures).
• Known allergic reactions or hypersensitivity to any component of the study medication in the nasal spray, such as E216, E218 and chlorobutanol hemihydrate.
• Participation in any (other) clinical trial with an investigational medicinal product or medical device within 3 months prior to randomisation.
• Current evidence of any mental or physical disorder or collaboration attitude which, in the judgment of the investigator makes the subject unsuitable for enrolment, and/or may interfere with the study evaluations or affect subject's safety.

Sponsors & Collaborators

• OptiNose AS: lead
• University of Oslo: collaborator

Study Sites (1)

Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research - TOP Study

Oslo, Norway

Location

Related Publications (3)

• Leknes S, Wessberg J, Ellingsen DM, Chelnokova O, Olausson H, Laeng B. Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions. Soc Cogn Affect Neurosci. 2013 Oct;8(7):741-9. doi: 10.1093/scan/nss062. Epub 2012 May 29.

  PMID: 22648957 BACKGROUND

• Quintana DS, Westlye LT, Alnaes D, Rustan OG, Kaufmann T, Smerud KT, Mahmoud RA, Djupesland PG, Andreassen OA. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial. Psychoneuroendocrinology. 2016 Jul;69:180-8. doi: 10.1016/j.psyneuen.2016.04.010. Epub 2016 Apr 22.

  PMID: 27107209 DERIVED

• Quintana DS, Westlye LT, Rustan OG, Tesli N, Poppy CL, Smevik H, Tesli M, Roine M, Mahmoud RA, Smerud KT, Djupesland PG, Andreassen OA. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment. Transl Psychiatry. 2015 Jul 14;5(7):e602. doi: 10.1038/tp.2015.93.

  PMID: 26171983 DERIVED

Related Links

• Click here for more information about NORMENT: Norwegian Centre for Mental Disorders Research

Study Officials

• Ole A Andreassen, MD

  University of Oslo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: November 14, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: April 23, 2014

Record last verified: 2014-04

Locations

NO (1)