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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Visit 1 Randomization | Experimental | 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. |
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| Visit 2: Crossover Randomization | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxytocin Intranasal Spray | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Obstructive Events | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vivek Jain, MD | The George Washington University | Principal Investigator |
| David Mendelowitz | The George Washington University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The GW Medical Faculty Associates | Washington D.C. | District of Columbia | 20037 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32862007 | Derived | 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. |
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At this time there is no plan to share IPD
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Experimental: Oxytocin, Then Placebo | At visit 1 (PSG 1) subjects first will receive Oxytocin Intranasal Spray (40 IU). 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. Then, at visit 2 (PSG 2), after a washout period of up to 4 weeks, they then received the Placebo Intranasal Spray: The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray. Subjects were blinded as to which drug they received first. |
| FG001 | Experimental: Placebo, Then Oxytocin | At visit 1 (PSG 1) subjects first will receive the Placebo Intranasal Spray: The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray. Then, at visit 2 (PSG 2), after a washout period of up to 4 weeks, they then received the receive Oxytocin Intranasal Spray (40 IU). 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. Subjects were blinded as to which drug they received first. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
There were 32 participants total, 16 in each arm.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Duration of Obstructive Events | Posted | Mean | Standard Deviation | seconds | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
|
6 weeks
There were no adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oxytocin | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Vivek Jain | Medical Faculty Associates at The George Washington University | 202-741-2676 | vjain@mfa.gwu.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Protocol w/ SAP | Dec 14, 2017 | Oct 31, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D020181 | Sleep Apnea, Obstructive |
| D012891 | Sleep Apnea Syndromes |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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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.
|
|
| Placebo Intranasal Spray | Drug | The placebo has been compounded to be an inactive, blinded comparative to the oxytocin nasal spray. |
|
|
| Assessed on Visit 1- Day 1, Visit 2- Day 29 |
| O2 Minimum | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body-mass Index | Mean | Standard Deviation | kg/m^2 |
|
| OG001 |
| Placebo |
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. |
|
|
| Secondary | Respiratory Rate | Posted | Mean | Standard Deviation | breaths per minute | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | proportion of events | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
|
|
|
| Secondary | O2 Minimum | Posted | Mean | Standard Deviation | % of Oxygen Saturation | Assessed on Visit 1- Day 1, Visit 2- Day 29 |
|
|
|
| 0 |
| 32 |
| 0 |
| 32 |
| 0 |
| 32 |
| EG001 | Placebo | 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. | 0 | 32 | 0 | 32 | 0 | 32 |
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |