Neuromodulation Therapy Device for the Treatment of Sleep Apnea

• ClinicalTrials.gov Identifier: NCT01117064
• Recruitment Status: Completed
• First Posted: May 5, 2010
• Last Update Posted: May 29, 2013
• Sponsor: Mayo Clinic
• Collaborator: Dymedix Corporation
• Information provided by (Responsible Party): John G. Park, Mayo Clinic

Study Description

Brief Summary:

We are looking to test a novel device in the treatment of Obstructive Sleep Apnea (OSA). Rather than using positive pressure to open the airways, we are testing a device that delivers an auditory tone to affect neuromodulation. We will test its efficacy in treating OSA while minimizing sleep disturbance. As this device is much less cumbersome to wear, we hope this therapy device will also improve compliance with treatment.

Condition or disease	Intervention/treatment	Phase
Obstructive Sleep Apnea	Device: Neuromodulation Therapy Device (NMTD)	Phase 1

Detailed Description:

Neuromodulation Therapy Device for the Treatment of Sleep Apnea

Obstructive sleep apnea (OSA) is a common public health problem with severe health consequences that substantially raises the risk of cardiovascular and cerebrovascular death. Continuous positive airway pressure (CPAP) is currently the most effective treatment option, yet up to half of patients fail to tolerate CPAP and require other approaches. Novel treatments offering alternatives to CPAP are thus sorely needed by those suffering from OSA. The Neuromodulation Therapy Device (NMTD) is a novel potential therapy for OSA. The main goal of our project is to evaluate the efficacy, tolerability, and safety of NMTD in patients with OSA.

Hypothesis 1 - The NMTD device is capable of reducing AHI.

OSA severity is indexed by apnea-hypopnea index (AHI), the number of apnea/hypopnea events occurring hourly during sleep. Our first aim is to determine NMTD's operating characteristics for treatment of OSA. The optimal duration of a detected apnea/hypopnea event before NMTD responds must first be determined. Additional adjustable features include sensitivity of respiratory event sensor, as well as pulse duration, frequency, and intensity of the delivered auditory tone. Since independent adjustment of each of the 4 parameters is not feasible, our screening analysis will test two variables at a time to identify which variables most effectively reduce AHI. This will allow for more practical titration during a therapeutic sleep study and more generalizable application of the device.

Hypothesis 2 - Modified NMTD is as effective and tolerable as CPAP in OSA treatment.

Once Aim 1 is complete and effective NMTD settings have been identified, we will initiate a Phase II NMTD trial to assess efficacy and tolerability. The primary outcome variable will be AHI reduction by NMTD compared with CPAP during a repeat polysomnogram (PSG). We will randomly assign previously titrated CPAP vs. NMTD to each subject then compare the resultant AHI between the two devices. Tolerability will also be assessed by sleep efficiency, arousal index, and sleep architecture. While auditory stimuli below 90 dB threshold should not adversely affect sleep architecture and quality,1 intermittent stimuli given during different sleep stages have not been previously assessed. Therefore, we will monitor NMTD's influence on sleep architecture, arousal index, and sleep efficiency compared to the same variables during CPAP use, allowing us to examine whether NMTD affects sleep quality. We will also assess patient preference in using CPAP versus NMTD.

Hypothesis 3 - NMTD will maintain efficacy with repeated use.

Given the brain's plasticity, it is unknown whether the brain may adapt to such repeated auditory stimuli. Constant auditory stimuli may lead to adaptation, resulting in the stimuli being "ignored." NMTD's stimuli, however, are less likely to lead to significant adaptation since they are intermittent and somewhat random, dependent on apneic or hypopneic events. Subjects will undergo two sequential nights of PSG with NMTD to evaluate if there is any stimulus-response extinction over time. In the future, when more devices are available, we will plan on long-term evaluations.

We propose to test this novel device in the treatment of OSA. This device, if successful, will substantially expand the treatment options for OSA by offering an effective alternative to CPAP with the potential for improved treatment compliance.

Plan:

This is a prospective study evaluating the efficacy of the NMTD in the treatment of OSA.

The study is divided into three consecutive phases, representing the three aims. If eligible, participants will be assigned to the phase that is currently being studied.

• One PSG, using the NMTD all night (32 participants)
• One PSG, split between the NMTD and standard CPAP therapy, randomized as to which is first (20 participants)
• Two consecutive PSGs using the NMTD all night (20 participants) to assess stimulus-response extinction over time (20 participants) All participants will complete a questionnaire about their experience with the device.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neuromodulation Therapy Device for the Treatment of Sleep Apnea
• Study Start Date: February 2010
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: NMTD adjustment testing; We will determine effective NMTD device settings for reducing AHI.	Device: Neuromodulation Therapy Device (NMTD); Subjects will have an overnight PSG using the NMTD. This device detects reduced airflow via a polymer sensor. When such event is detected, a short burst of sound is administered via earphones. We will determine NMTD's operating characteristics for treatment of OSA. The optimal duration of a detected apnea/hypopnea event before NMTD responds must first be determined. Additional adjustable features include sensitivity of respiratory event sensor, as well as pulse duration, frequency, and intensity of the delivered auditory tone. Since independent adjustment of each of the 4 parameters is not feasible, our screening analysis will test two variables at a time to identify which variables most effectively reduce AHI.
Active Comparator: CPAP vs NMTD device; We will randomly assign previously titrated CPAP vs. NMTD to each subject then compare the resultant AHI between the two devices.	Device: Neuromodulation Therapy Device (NMTD); Subjects will have an overnight PSG using CPAP (as previously titrated) for half of the night and NMTD the other half (this order will be randomized). we will monitor NMTD's influence on Apnea Hypopnea Index (AHI), sleep architecture, arousal index, and sleep efficiency compared to the same variables during CPAP use
Active Comparator: NMTD efficacy and tolerability; Subjects will undergo two sequential nights of PSG with NMTD to evaluate if there is any stimulus-response extinction over time.	Device: Neuromodulation Therapy Device (NMTD); Subjects will undergo two sequential nights of PSG with NMTD to evaluate if there is any stimulus-response extinction over time.

Outcome Measures

Primary Outcome Measures :

1. We will determine effective device settings on the Neuromodulation Therapy Device (NMTD). [ Time Frame: First year ]

Secondary Outcome Measures :

1. We will compare the modified NMTD's efficacy and tolerability to that of CPAP in treating OSA. [ Time Frame: Second year ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects 18 years or older
• Completed a comprehensive Sleep Medicine evaluation and a standard split-night polysomnogram
• Able to give informed consent
• Confirmed diagnosis of OSA
• Positive airway pressure device naive

Exclusion Criteria:

• Unsuccessful CPAP titration
• Inability to detect screening tone in either ear without the use of hearing aid
• Inability to tolerate a 37 dB tone
• Need for nocturnal oxygen or non-invasive positive pressure ventilation due to hypoventilation/hypercapnia
• Predominantly mixed or central apneas or those who develop complex sleep apnea during the PSG
• Neurologic disorders such as seizure disorder or narcolepsy
• Psychiatric disorders currently not under adequate control
• Need for nurse or other's assistance during the night due to problems of nocturnal confusion, delirium, or other conditions that would preclude the subject from wearing the device all night
• Pregnancy (will be tested)

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Dymedix Corporation

Investigators

• Principal Investigator: John G. Park, M.D.; Mayo Clinic

More Information

• Responsible Party: John G. Park, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01117064
• Other Study ID Numbers: 09-006804
• First Posted: May 5, 2010
• Last Update Posted: May 29, 2013
• Last Verified: May 2013

Keywords provided by John G. Park, Mayo Clinic:

Sleep Apnea; OSA; CPAP

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases