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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
Sponsor:
Collaborator:
University of Oslo
Information provided by (Responsible Party):
OptiNose AS

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.


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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
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

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
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)
Drug: Placebo
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



Primary Outcome Measures :
  1. 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

  2. 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).

  3. 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.

  4. Aim 1d: Eyetracking [ Time Frame: 20 minutes after oxytocin placebo administration ]
    An eyetracking device will measure eyegaze and pupillometry.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Oxytocin levels in saliva [ Time Frame: 20 prior to fMRI procedure ]
    Saliva will be collected for pharmacokinetic analysis of oxytocin and cortisol in saliva.

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 35 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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:

    1. Heart rate: 40 to 90 beats per minute
    2. Systolic blood pressure (BP): 90 to 140 mmHg
    3. Diastolic BP: 50 to 90 mmHg
    4. Oral temperature: 36.0 to 37.5°C
    5. 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.

Exclusion Criteria:

An ear, nose and throat (ENT) specialist will inspect the noses of all individuals who enter the study.

In order to participate in the study subjects must not meet any of the following exclusion criteria;

  • 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.
  • Subjects with any metal implants.
  • Subjects with claustrophobia.
  • Other unspecified reasons that, in the opinion of the Investigator or the sponsor make the subject unsuitable for enrolment.
  • Subjects with female partners of child-bearing potential must use an adequate form of contraception prior to entry into the study until three months following the post-study medical visit. Subjects must not have a partner who is either pregnant or breastfeeding for the duration of the study. Adequate contraception is defined as the usage by the female partner of any form of hormonal contraception or intra-uterine device (which should be established prior to the start of the study) plus usage by one of the partners of an additional spermicide- containing barrier method of contraception.

Information from the National Library of Medicine

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


Locations
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Norway
Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research - TOP Study
Oslo, Norway
Sponsors and Collaborators
OptiNose AS
University of Oslo
Investigators
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Principal Investigator: Ole A Andreassen, MD University of Oslo
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: OptiNose AS
ClinicalTrials.gov Identifier: NCT01983514    
Other Study ID Numbers: SMR-2727
First Posted: November 14, 2013    Key Record Dates
Last Update Posted: April 23, 2014
Last Verified: April 2014
Keywords provided by OptiNose AS:
oxytocin
fMRI
social cognition
heart rate variability
pupillometry
eye tracking
Additional relevant MeSH terms:
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Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs