Clinical trial NCT03844295: Obstructive Sleep Apnea Therapy by Stimulation of the Hypoglossal Nerve
Official title: Upper AIRway Implanted Nerve STIMulation Therapy: A Breakthrough in Obstructive Sleep Apnea Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea Syndrome
Keywords: stimulation
hypoglossal nerve
Upper-airway
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Inspire Medical Systems, Inc.
First posted: 2019-02-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Monocentric, prospective, controlled, patient single-blind study
Primary purpose: TREATMENT

Brief summary: Continuous positive airway pressure (CPAP) is the gold standard to normalize breathing during sleep in patients with obstructive sleep apnea syndrom (OSA). Many patients will not tolerate or will not accept CPAP. Implanted nerve stimulation is a novel therapy for OSA patients that restores the upper airway potency using unilateral XII nerve electric stimulation.

The principal objective of this study is short-term efficacy of a new treatment for OSA on blood pressure variability during sleep.

Detailed description: Obstructive sleep apnea (OSA) syndrome had become over the last decade a serious health concern due to its high prevalence which raise 10% of the general population.

It is characterized by recurrent episodes of airflow obstruction in the upper airway (UA) consequence of passive collapse of the UA, particularly at the tongue level. These collapses induce recurrent asphyxia that results in oxygen desaturations with persistant and crescendo respiratory efforts inducing arousals from sleep.

Indeed, despite its large efficacy some of the patients will never accept continuous positive airway pressure treatment or will not tolerate. To this extent, alternative treatement has been developed: implanted hypoglossal stimulation. This treatment has been developed by Inspire Medical Device. The Inspire® system is intended to prevent base-of-tongue obstruction as well as specific soft palate obstructions by stimulating the hypoglossal nerve synchronous with respiration.

A selection processus will be applied in order to identify the patients that will be good responders to the hypoglossal stimulation.

The main criterion of selection is based on Drug Induced Sleep Endoscopy(DISE) that will be performed by a trained endoscopist dedicated to this study.

This sleep endoscopy allows to visualize during induced sleep the shape of the UA and the type of collapsus. Indeed an antero-posterior collapsus is related to a good response to hypoglossal nerve stimulation while complete concentric obstruction at velopharyngeal is a predictor of poor response.

In this pilot study, the investigators evaluate as a primary outcome the delta range of blood pressure during sleep but also other cardiovascular indexes targeting blood pressure and heart rate variability as secondary outcomes.

Eligibility criteria: Inclusion Criteria:

* Patient aged 18 to 80 years old
* Patient with moderate to severe OSA based on an established diagnosis of OSA (15≤AHI\<65) by polysomnography or respiratory polygraphy not older thant three years.
* Patient with moderate to severe OSA naïve of treatment or with difficulty accepting or adhering to CPAP treatment.
* Willing and capable to have stimulation hardware permanently implanted, and to use the patient programmer to activate the stimulation
* Willing and capable to return for all follow-up visits and conduct sleep studies at home, including the evaluation procedures and filling out questionnaires
* Willing and capable of providing written informed consent.

Exclusion Criteria:

* Any anatomical finding that would compromise the performance of upper airway stimulation, such as the presence of complete concentric collapse of the soft palate
* Have any condition or procedure that has compromised neurological control of the upper airway
* Unable to operate the patient programmer
* Pregnant or plan to become pregnant, and breastfeeding women
* Require magnetic resonance imaging (MRI)
* Have an implantable device that may be susceptible to unintended interaction with the Inspire system.

Additional exclusions for study purposes only

* Body Mass Index (BMI) of \>32
* Central + mixed apneas \> 25% of the total apnea-hypopnea index (AHI)
* Neuromuscular disease
* Hypoglossal-nerve palsy
* Severe restrictive or obstructive pulmonary disease
* Moderate-to-severe pulmonary arterial hypertension
* Severe valvular heart disease
* New York Heart Association class III or IV heart failure
* Recent myocardial infarction or severe cardiac arrhythmias (within the past 6 months)
* Persistent uncontrolled hypertension despite medication use
* Coexisting nonrespiratory sleep disorders that would confound functional sleep assessment
* Any chronic medical illness or condition that contraindicates a surgical procedure under general anesthesia, as judged by the clinical study Investigator
* a terminal illness with life expectancy \< 12 months
* Active psychiatric disease (psychotic illness, major depression, or acute anxiety attacks) which prevents subject compliance with the requirements of the investigational study testing
* Radiotherapy or ablation therapy of the head and/or neck
* Surgical resection for cancer or congenital malformations in the larynx, tongue, or throat(with exception of tonsillectomy and/or adenoidectomy)
* Previous surgery within 3 months performed on the soft-palate tissue
* Obvious fixed upper airway obstructions (tumors, polyps, unilateral nasal obstruction)
* Need for chronic supplemental oxygen therapy for any other reason, pO2 (partial pressure of oxygen) \< 55 mm Hg
* Clinical evidence of severe renal failure (Stage 4 or 5) undergoing dialysis or expected to institute dialysis within 6 months
* Patients on medication that may alter consciousness, the pattern of respiration or sleep architecture (for example, benzodiazepiones, opiates, neuroleptics, prescription stimulants, phenothiazine, or any form of chemical substance abuse)
* Patients taking blood thinning medications (for example warfarin, aspirin, plavix or other blood thinning agents which cannot be safety stopped or bridged temporarily to allow surgery to take place)
* Any other reason for the investigator deems that the subject is unfit for participation in the study
* Subject in exclusion period for another study
* Subject under administrative or judicial control.

Primary outcomes:
measure: Short-term efficacy of a new treatment for OSA on systolic blood pressure variability during sleep
timeFrame: one month treatment active versus non active treatment
Secondary outcomes:
measure: Short-term efficacy of a new treatment for OSA on mean-24h, daytime and nighttime blood pressure
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on OSA by Epworth sleepiness scale score
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on Apnea-Hypopnea Index measured by polysomnography
timeFrame: one month treatment active versus non active treatment
measure: Change in sympatho-vagal balance based on heart rate variability analysis
timeFrame: one month treatment active versus non active treatment
measure: Self-reported changes in sleep and quality of life by SF-36 score
timeFrame: one month treatment active versus non active treatment
measure: Sleep latency assessed during a Maintenance of Wakefulness Test
timeFrame: one month treatment active versus non active treatment
measure: Nocturnal pulse pressure assessed by Continuous Non-invasive Arterial Pressure monitoring
timeFrame: one month treatment active versus non active treatment
measure: Short-term efficacy of a new treatment for OSA on diastolic blood pressure variability during sleep
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on OSA by Pichot weakness scale score
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on nocturia
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on morning asthenia
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on morning headache
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on snoring
timeFrame: one month treatment active versus non active treatment
measure: Self-reported changes in sleep and quality of life by FOSQ score
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on oxygen desaturation index measured by polysomnography
timeFrame: one month treatment active versus non active treatment
measure: Clinical efficacy of this new treatment on sleep efficacy measured by polysomnography
timeFrame: one month treatment active versus non active treatment
Other outcomes:
Locations:
city: Grenoble
country: France
facility: UniversityHospitalGrenoble
Study officials:
affiliation: University Hospital, Grenoble
name: Renaud RT TAMISIER, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993 Apr 29;328(17):1230-5. doi: 10.1056/NEJM199304293281704.
citation: Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002 May 1;165(9):1217-39. doi: 10.1164/rccm.2109080.
citation: Mulgrew AT, Ryan CF, Fleetham JA, Cheema R, Fox N, Koehoorn M, Fitzgerald JM, Marra C, Ayas NT. The impact of obstructive sleep apnea and daytime sleepiness on work limitation. Sleep Med. 2007 Dec;9(1):42-53. doi: 10.1016/j.sleep.2007.01.009. Epub 2007 Sep 6.
citation: Lallukka T, Kaikkonen R, Harkanen T, Kronholm E, Partonen T, Rahkonen O, Koskinen S. Sleep and sickness absence: a nationally representative register-based follow-up study. Sleep. 2014 Sep 1;37(9):1413-25. doi: 10.5665/sleep.3986.
citation: Tamisier R, Pepin JL, Remy J, Baguet JP, Taylor JA, Weiss JW, Levy P. 14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans. Eur Respir J. 2011 Jan;37(1):119-28. doi: 10.1183/09031936.00204209. Epub 2010 Jun 4.
citation: Pepin JL, Tamisier R, Barone-Rochette G, Launois SH, Levy P, Baguet JP. Comparison of continuous positive airway pressure and valsartan in hypertensive patients with sleep apnea. Am J Respir Crit Care Med. 2010 Oct 1;182(7):954-60. doi: 10.1164/rccm.200912-1803OC. Epub 2010 Jun 3.
citation: Gagnadoux F, Fleury B, Vielle B, Petelle B, Meslier N, N'Guyen XL, Trzepizur W, Racineux JL. Titrated mandibular advancement versus positive airway pressure for sleep apnoea. Eur Respir J. 2009 Oct;34(4):914-20. doi: 10.1183/09031936.00148208. Epub 2009 Mar 26.
citation: Strollo PJ Jr, Soose RJ, Maurer JT, de Vries N, Cornelius J, Froymovich O, Hanson RD, Padhya TA, Steward DL, Gillespie MB, Woodson BT, Van de Heyning PH, Goetting MG, Vanderveken OM, Feldman N, Knaack L, Strohl KP; STAR Trial Group. Upper-airway stimulation for obstructive sleep apnea. N Engl J Med. 2014 Jan 9;370(2):139-49. doi: 10.1056/NEJMoa1308659.
citation: Mayer P, Pepin JL, Bettega G, Veale D, Ferretti G, Deschaux C, Levy P. Relationship between body mass index, age and upper airway measurements in snorers and sleep apnoea patients. Eur Respir J. 1996 Sep;9(9):1801-9. doi: 10.1183/09031936.96.09091801.
citation: Eastwood PR, Barnes M, Walsh JH, Maddison KJ, Hee G, Schwartz AR, Smith PL, Malhotra A, McEvoy RD, Wheatley JR, O'Donoghue FJ, Rochford PD, Churchward T, Campbell MC, Palme CE, Robinson S, Goding GS, Eckert DJ, Jordan AS, Catcheside PG, Tyler L, Antic NA, Worsnop CJ, Kezirian EJ, Hillman DR. Treating obstructive sleep apnea with hypoglossal nerve stimulation. Sleep. 2011 Nov 1;34(11):1479-86. doi: 10.5665/sleep.1380.
citation: Goding GS Jr, Tesfayesus W, Kezirian EJ. Hypoglossal nerve stimulation and airway changes under fluoroscopy. Otolaryngol Head Neck Surg. 2012 Jun;146(6):1017-22. doi: 10.1177/0194599812436472. Epub 2012 Feb 3.
citation: Schwartz AR, Barnes M, Hillman D, Malhotra A, Kezirian E, Smith PL, Hoegh T, Parrish D, Eastwood PR. Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea. Am J Respir Crit Care Med. 2012 Feb 15;185(4):420-6. doi: 10.1164/rccm.201109-1614OC. Epub 2011 Dec 1.
citation: Mwenge GB, Dury M, Delguste P, Rodenstein D. Response of automatic continuous positive airway pressure devices in a normal subject. Eur Respir J. 2011 Jun;37(6):1530-3. doi: 10.1183/09031936.00139510. No abstract available.
citation: Oldenburg O, Lamp B, Faber L, Teschler H, Horstkotte D, Topfer V. Sleep-disordered breathing in patients with symptomatic heart failure: a contemporary study of prevalence in and characteristics of 700 patients. Eur J Heart Fail. 2007 Mar;9(3):251-7. doi: 10.1016/j.ejheart.2006.08.003. Epub 2006 Oct 5.
citation: Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest. 1995 Oct;96(4):1897-904. doi: 10.1172/JCI118235.
citation: Tamisier R, Tan CO, Pepin JL, Levy P, Taylor JA. Blood Pressure Increases in OSA due to Maintained Neurovascular Sympathetic Transduction: Impact of CPAP. Sleep. 2015 Dec 1;38(12):1973-80. doi: 10.5665/sleep.5252.
citation: Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, Marcus CL, Mehra R, Parthasarathy S, Quan SF, Redline S, Strohl KP, Davidson Ward SL, Tangredi MM; American Academy of Sleep Medicine. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2012 Oct 15;8(5):597-619. doi: 10.5664/jcsm.2172.