The Effect of Mandibular Advancement Devices on Markers of Cardiovascular Health in Obstructive Sleep Apnea Patients

March 11, 2024 updated by: University of Alberta

The Effect of Mandibular Advancement Devices on Markers of Cardiovascular Health in Mild to Moderate Obstructive Sleep Apnea Patients Who Are Non-Compliant With Continuous Positive Airway Pressure Therapy

Obstructive sleep apnea (OSA) is a type of disordered breathing defined by the repetitive obstruction of airflow during sleep due to upper airway collapse. Each obstructive event contributes to decreased blood oxygen, or hypoxia. OSA has been associated with various cardiovascular diseases, including hypertension, stroke, heart failure, and coronary artery disease. A factor in this association may be the decrease in blood vessel health and the marked over activation of the sympathetic nervous system that is observed in OSA due to nighttime hypoxia. The sympathetic nervous system is responsible for maintaining heart and blood vessel (cardiovascular) balance. Elevated sympathetic nervous activity (SNA) is a likely cause of hypertension and subsequent cardiovascular disease.

Continuous positive airway pressure (CPAP) therapy is the most accepted treatment for OSA and has been shown to improve high blood pressure and SNA in patients. An alternative therapy for OSA is a type of removable oral appliance known as a mandibular advancement device (MAD). Currently, there is no research directly measuring SNA in OSA patients using MADs. In addition to other cardiovascular markers, the investigators would like to directly assess SNA during a MAD intervention using the gold standard technique of microneurography. The investigators believe this will provide important information for the management of OSA, as levels of SNA are known to respond to both acute and chronic levels of hypoxia. Improved heart and blood vessel markers could further support MAD use, providing an important alternative therapy for those that can not tolerate CPAP.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In OSA the obstruction of breathing can be either partial (hypopnea) or complete (apnea), and each obstructive event contributes to decreased blood oxygen, or hypoxia. Sleep disordered breathing and nighttime hypoxia have both been identified as independent risk factors of death. Specifically, OSA is estimated to affect 34% of men and 17% of women and when inadequately treated patients present with daytime sleepiness, depression, workplace accidents and cardiovascular disease.

The severity of OSA is determined by the apnea-hypopnea index (AHI) which is the average number of airway obstructions experienced per hour of sleep. CPAP therapy has been shown to improve high blood pressure, AHI and SNA in patients. However, benefits of CPAP therapy are dose-dependent and are largely affected by patient compliance. Unfortunately, due to various discomforts associated with the use of CPAP therapy, less than fifty percent of patients adhere to long-term therapy.

MADs have increased compliance in comparison to CPAP, and improve some patient's symptoms of sleepiness. Yet, MAD interventions have shown smaller improvements in AHI values when compared to CPAP. However, AHI has been criticized for being an overly simplistic measurement of nocturnal hypoxia. In contrast, SNA is known to respond both acutely and chronically to varying levels of blood oxygen. Therefore, MAD interventions may not produce changes in AHI equal to that of a CPAP intervention; however, they may change levels of SNA and other specific CV markers of blood vessel health. This would further support the use of MADs and provide additional insight into the underlying cardiovascular mechanisms involved in OSA therapy. Understanding and validating additional therapies for OSA is of great importance, due to the significant health consequences of the disease.

Objectives

The proposed investigation aims to determine the following in mild to moderate OSA patients who fail to comply with CPAP therapy:

Does MAD therapy improve AHI in mild to moderate severity OSA?

Does MAD therapy lower basal SNA in mild to moderate severity OSA?

Does MAD therapy improve vascular function, blood pressure, heart rate variability and blood markers of elevated SNA in mild to moderate severity OSA?

Research Method/ Procedures

Methodology

To address this hypothesis, the investigators propose a prospective case series examining subjects at baseline, at 3 months and again at 6 months after a MAD intervention. A 2020 study by Ruzicka et al. found no changes in SNA after a CPAP intervention of 6 weeks. Another study by Henderson et al, 2016, found a significant reduction in SNA during a CPAP intervention of 6 months and 12 months. In 2009, Kuramoto et al measured changes in SNA indirectly during a 3 month CPAP intervention and did not see significant results. Our methodology involves direct measurement of SNA during MAD therapy, therefore, testing intervals at baseline, 3 months and 6 months of MAD therapy have been selected.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2R3
        • Recruiting
        • University of Alberta
        • Contact:
        • Contact:
        • Principal Investigator:
          • Carlos F Mir, DSc
        • Sub-Investigator:
          • Emily King, MSc, DDS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Volunteers with mild to moderate OSA will be recruited with the assistance of referring dentists who are certified to provide MADs under the Alberta Dental Association & College guidelines. Participants will be included if they are between the ages of 18-70 years, initiating adjustable MAD therapy with their provider and no medical history of heart failure, cardiopulmonary and renal disease

Description

Inclusion Criteria:

  • Between ages of 18-70
  • Diagnosed with Obstructive Sleep Apnea and prescribed with Mandibular Advancement Device
  • No medical history of cardiovascular, pulmonary, renal diseases

Exclusion Criteria:

  • Any known cardiovascular, respiratory or pulmonary disease
  • Have a history of smoking regularly in past 6 months
  • Pre-existing symptomatic non-respiratory sleep disorder (restless leg syndrome, chronic insomnia)
  • if more than 50% of their observed apneas are due to sleep apnea

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in Sympathetic Nerve Activity
Time Frame: 3 months
Muscle sympathetic nerve activity. Direct multi-unit postganglionic muscle sympathetic nerve activity (MSNA) will be obtained via microneurography. A sterile Tungsten recording microelectrode (35 mm long, 200 μm in diameter, tapered to a 1- to 5-μm uninsulated tip) will be inserted into a muscle nerve fascicle of a sympathetic nerve bundle, of the peroneal nerve. A reference electrode will also be inserted subcutaneously 1-3 cm from the recording electrode. MSNA will be obtained by manually manipulating the microelectrode until a characteristic bursting pattern is observed A trained researcher will record and analyze to quantify sympathetic activity as: burst frequency (bursts/min), burst incidence (bursts/ 100 heart beats), burst amplitude (normalized to largest resting amplitude), and total activity (burst frequency multiplied by mean normalized burst amplitude)
3 months
Difference in Cardiovascular markers - Heart Rate
Time Frame: 3 months
All cardiovascular parameters will be acquired using an analog-to-digital converter (Powerlab/16SP ML 880; ADInstruments, Colorado Springs, CO, USA) interfaced with a personal computer. Commercially available software will be used to analyze ventilatory and cardiovascular variables (LabChart V7.1, ADinstruments, Colorado Springs, CO, USA). Throughout all procedures, heart rate will be determined from a standard lead III electrocardiogram (ML 132, ADInstruments, Colorado Springs, CO, USA). Heart Rate will be recorded in beats/ minute
3 months
Difference in Cardiovascular markers- Blood Pressure
Time Frame: 3 months
All cardiovascular parameters will be acquired using an analog-to-digital converter (Powerlab/16SP ML 880; ADInstruments, Colorado Springs, CO, USA) interfaced with a personal computer. Commercially available software will be used to analyze ventilatory and cardiovascular variables (LabChart V7.1, ADinstruments, Colorado Springs, CO, USA). Throughout all procedures, Blood pressure will be recorded beat-by-beat by finger pulse photoplethysmograph; mmHg.
3 months
Fasted blood sample- Neurotransmitters
Time Frame: 3 months
Fasted blood samples (~30ml) will be analyzed for sympathetic nervous system neurotransmitters (Norepinephrine, Epinephrine,)
3 months
Fasted blood sample- Sex Hormones
Time Frame: 3 months
Fasted blood samples (~30ml) will be analyzed for sex hormones (estrogen, progesterone, testosterone)
3 months
Endothelial function- time to peak dilation
Time Frame: 3 months
Flow Mediated Dilation: This will be assessed in the brachial artery, using an ultrasound system. A sphygmomanometer cuff will be placed and inflated around the forearm to a supra-systolic pressure (250 mmHg) to occlude forearm blood flow for 5 min. After this time period, the cuff will be rapidly deflated (~1 s). Baseline brachial artery blood flow velocity and diameter will be recorded for 1 minute before cuff inflation, and for 3.5 min beginning 30 s prior to cuff release. (FMD, time to maximal dilation; s)
3 months
Endothelial function- Flow mediated dilation
Time Frame: 3 months
Flow Mediated Dilation: This will be assessed in the brachial artery, using an ultrasound system. A sphygmomanometer cuff will be placed and inflated around the forearm to a supra-systolic pressure (250 mmHg) to occlude forearm blood flow for 5 min. After this time period, the cuff will be rapidly deflated (~1 s). Baseline brachial artery blood flow velocity and diameter will be recorded for 1 minute before cuff inflation, and for 3.5 min beginning 30 s prior to cuff release. Percent change in artery diameter will be calculated.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Alberta

Investigators

  • Principal Investigator: Craig Steinback, PhD, University of Alberta
  • Principal Investigator: Carlos F Mir, DSc, University of Alberta

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2021

Primary Completion (Estimated)

July 31, 2024

Study Completion (Estimated)

July 31, 2024

Study Registration Dates

First Submitted

March 29, 2022

First Submitted That Met QC Criteria

May 18, 2022

First Posted (Actual)

May 24, 2022

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00108618

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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