Impact of Oxytocin on Obstructive Sleep Apnea Induced Changes in Sleep

In human volunteers intranasal administration of oxytocin significantly increases parasympathetic and decreases sympathetic cardiac control. OSA is a very prevalent disease with high cardiovascular risk factors, yet this disease remains very poorly treated.

This proposal, based on the current literature and new basic science results detailed above on the role of oxytocin in cardiovascular control, will test if oxytocin administration improves adverse cardiovascular events during the recurrent nocturnal apneas in patients with OSA. This project will lay the groundwork and provide preliminary data to obtain NIH funding to test this important hypotheses more thoroughly and in larger clinical trials.

This study will explore if intranasal oxytocin has any positive cardiovascular benefits in patients with sleep apnea.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Drug: Oxytocin Intranasal Spray; Drug: Placebo Intranasal Spray

Detailed Description

Obstructive Sleep Apnea (OSA) is a major, yet poorly understood cardiovascular health risk that occurs in as many as 24% of males and 9% of females within the US population. OSA can participate in both the initiation and progression of several cardiovascular diseases including sudden death, hypertension, arrhythmias, myocardial ischemia and stroke.

Many of the adverse cardiovascular consequences of OSA are thought to be associated with a diminished cardiac vagal activity, as parasympathetic cardiac vagal activity is typically cardio-protective. Intranasal administration of oxytocin has been shown to significantly increase parasympathetic and decrease sympathetic cardiac control. In this research study, the effect oxytocin has on changes in heart rate or other Polysomnography (PSG) measures in a group of patients that have recently been diagnosed with OSA will be examined.

OSA is typically diagnosed through a polysomnography, a comprehensive recording of the biophysiological changes that occur during sleep. The PSG monitors many body functions including brain (EEG), eye movements (EOG), muscle activity or skeletal muscle activation (EMG) and heart rhythm (ECG) during sleep, respiratory airflow, respiratory effort, pulse oximetry etc.

In this research study, subjects who have recently been diagnosed with OSA will undergo two research study PSGs. Before the first study PSG, subjects will be randomized to receive either Oxytocin (40 IU) or placebo, in a blinded manner, prior to beginning the test. The PSG will then continue as usual, and subject data pertaining to the PSG will be gathered. Subjects will then return within 4 weeks for a second research PSG, where one hour before the test they will receive the opposite intervention that they did not received during the first research PSG study. Data measurements will be re-measured and compared between the two PSGs.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • The GW Medical Faculty Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women 18 years old or older of any ethnic background
• Subjects that have recently undergone a standard "in the sleep-lab" diagnostic polysomnography (per standard of care medical guidelines), or the "at home" diagnostic test, and have been diagnosed with OSA

Exclusion Criteria:

• Pregnant or Breastfeeding women
• Women of Child Bearing Potential who are not willing to undergo methods to prevent pregnancy
• Subjects who are on medications that affect cardiac autonomic function (eg. Beta Blockers)
• Active smokers
• Subjects who are unable to read or answer questions in the English language

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Visit 1 Randomization; At visit 1 (PSG 1) subjects will receive one of two interventions: either Oxytocin Intranasal Spray (40 IU) or Placebo Intranasal Spray. Subjects will be blinded as to which drug they are receiving.	Drug: Oxytocin Intranasal Spray; In human volunteers intranasal administration of oxytocin significantly increases parasympathetic and decreases sympathetic cardiac control. In addition to the classic effects of oxytocin on uterine contraction and milk ejection, recent work indicates oxytocin is present in both males and females and has an important role in both behavior and cardiovascular homeostasis, particularly during anxiety and stress.; Other Names: Synotocin; Drug: Placebo Intranasal Spray; The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray.; Other Names: Placebo
EXPERIMENTAL: Visit 2: Crossover Randomization; At visit 2 (PSG 2) subjects will receive the opposite intervention from the one they received at visit 1: either Oxytocin Intranasal Spray (40 IU) or Placebo Intranasal Spray. Subjects will be blinded as to which drug they are receiving.	Drug: Oxytocin Intranasal Spray; In human volunteers intranasal administration of oxytocin significantly increases parasympathetic and decreases sympathetic cardiac control. In addition to the classic effects of oxytocin on uterine contraction and milk ejection, recent work indicates oxytocin is present in both males and females and has an important role in both behavior and cardiovascular homeostasis, particularly during anxiety and stress.; Other Names: Synotocin; Drug: Placebo Intranasal Spray; The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Duration of Obstructive Events	Assessed on Visit 1- Day 1, Visit 2- Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory Rate		Assessed on Visit 1- Day 1, Visit 2- Day 29
Incidence Proportion of Bradycardia	Event-associated bradycardias were identified as a heart rate reduction of 5 bpm or more from the average heart rate during the 5 s preceding an event to the lowest heart rate either during an event or within 5 s immediately after an event. Incidence proportion, or risk, of bradycardia was calculated as follows: the number of events that resulted in bradycardia divided by the total number of events. This analysis was done using custom MATLAB (MathWorks) code to study heart rate and peripheral capillary oxyhemoglobin saturation (SPO2) before and after apnea and hypopnea events.	Assessed on Visit 1- Day 1, Visit 2- Day 29
O2 Minimum		Assessed on Visit 1- Day 1, Visit 2- Day 29

Collaborators and Investigators

• Sponsor: George Washington University
• Investigators: Principal Investigator: David Mendelowitz, The George Washington University

Publications and helpful links

General Publications

• Jain V, Kimbro S, Kowalik G, Milojevic I, Maritza Dowling N, Hunley AL, Hauser K, Andrade DC, Del Rio R, Kay MW, Mendelowitz D. Intranasal oxytocin increases respiratory rate and reduces obstructive event duration and oxygen desaturation in obstructive sleep apnea patients: a randomized double blinded placebo controlled study. Sleep Med. 2020 Oct;74:242-247. doi: 10.1016/j.sleep.2020.05.034. Epub 2020 Jun 5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 27, 2016
• Primary Completion (ACTUAL): June 7, 2020
• Study Completion (ACTUAL): June 7, 2020

Study Registration Dates

• First Submitted: March 30, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (ACTUAL): May 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Sleep Apnea; Oxytocin Nasal Spray
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: GWU_IRB_041333

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this time there is no plan to share IPD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No