Sleep Apnea, Obstructive
Conditions
Keywords
Sleep Apnea, Oxytocin Nasal Spray
Brief summary
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.
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.
Interventions
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.
The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray.
Sponsors
Study design
Masking description
All members of the research team except the IP dispensing staff will be blinded for the duration of the research study. Once all the subjects have finished in the research study, and all data is data-locked, the outcomes assessor will then unblind the research data for the statistical analysis.
Eligibility
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Duration of Obstructive Events | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory Rate | Assessed on Visit 1- Day 1, Visit 2- Day 29 | — |
| Incidence Proportion of Bradycardia | Assessed on Visit 1- Day 1, Visit 2- Day 29 | 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. |
| O2 Minimum | Assessed on Visit 1- Day 1, Visit 2- Day 29 | — |
Countries
United States
Participant flow
Pre-assignment details
36 subjects with OSA were assessed for eligibility and willingness to participate in this double blinded cross over placebo-controlled trial. Four subjects declined to participate. The remaining 32 subjects were randomly assigned to receive either placebo (n=16) or oxytocin (n=16) in the first visit, then a washout period within 4 weeks, then the other intervention they did not receive in the second visit.
Participants by arm
| Arm | Count |
|---|---|
| Oxytocin, Then Placebo 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.
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.
Placebo Intranasal Spray: The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray. | 16 |
| Placebo, Then Oxytocin 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.
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.
Placebo Intranasal Spray: The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray. | 16 |
| Total | 32 |
Baseline characteristics
| Characteristic | Oxytocin, Then Placebo | Placebo, Then Oxytocin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 16 Participants | 32 Participants |
| Age, Continuous | 42.8 years STANDARD_DEVIATION 9.1 | 42.8 years STANDARD_DEVIATION 9.1 | 42.8 years STANDARD_DEVIATION 9.1 |
| Body-mass Index | 31.8 kg/m^2 STANDARD_DEVIATION 8.7 | 31.8 kg/m^2 STANDARD_DEVIATION 8.7 | 31.8 kg/m^2 STANDARD_DEVIATION 8.7 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 7 Participants | 7 Participants | 14 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Duration of Obstructive Events
Time frame: Assessed on Visit 1- Day 1, Visit 2- Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Duration of Obstructive Events | 22.72 seconds | Standard Deviation 4.59 |
| Placebo | Duration of Obstructive Events | 24.66 seconds | Standard Deviation 5.12 |
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.
Time frame: Assessed on Visit 1- Day 1, Visit 2- Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Incidence Proportion of Bradycardia | 0.08 proportion of events | Standard Deviation 0.07 |
| Placebo | Incidence Proportion of Bradycardia | 0.14 proportion of events | Standard Deviation 0.07 |
O2 Minimum
Time frame: Assessed on Visit 1- Day 1, Visit 2- Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | O2 Minimum | 94.31 % of Oxygen Saturation | Standard Deviation 1.8 |
| Placebo | O2 Minimum | 92.44 % of Oxygen Saturation | Standard Deviation 4.24 |
Respiratory Rate
Time frame: Assessed on Visit 1- Day 1, Visit 2- Day 29
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oxytocin | Respiratory Rate | 17.39 breaths per minute | Standard Deviation 3.5 |
| Placebo | Respiratory Rate | 16.69 breaths per minute | Standard Deviation 3.24 |