Combination Therapy to Treat Sleep Apnea

NCT01633827 | Completed Results

• 2 other identifiers: BWH-2012P0009565R01HL102321-02
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

In Obstructive sleep apnea (OSA), the upper airway closes over and over again during sleep. This leads to disrupted sleep (waking up during the night), daytime sleepiness, and an increased risk for developing high blood pressure. Currently, the best treatment for obstructive sleep apnea is sleeping with a mask that continuously blows air into the nose (i.e. Continuous positive airway pressure \[CPAP\] treatment). While CPAP treatment stops the upper airway from closing in most people, many people have difficulty sleeping with the mask in place and therefore do not use the CPAP treatment. This research study is being conducted to learn whether using a combination of therapies (i.e. a sedative and oxygen therapy) will improve OSA severity by altering some of the traits that are responsible for the disorder.

Conditions

Sleep Apnea, Obstructive

Outcome Measures

Primary Outcomes (4)

• Model Prediction of Absence/Presence of OSA: Ventilation That Causes an Arousal From Sleep (Varousal)

  Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual. In this table the investigators report the minimum ventilation that can be tolerated before an arousal from sleep (Varousal). It is calculated by slowly reducing the CPAP level from optimum to the minimum tolerable pressure. This trait is symbolized as Varousal (L/min)

  Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

• Model Prediction of Absence/Presence of OSA: Ventilatory Control Sensitivity (Loop Gain)

  Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. In this table the investigators report the ventilatory control sensitivity value (Loop Gain). It is calculated dividing the increase in ventilatory drive by the steady state reduction in ventilation. The increase in ventilatory drive is measured as the ventilatory overshoot following a switch to optimal CPAP from the minimum tolerable CPAP. This trait is symbolized as steady state loop gain (LG, adimensional)

  Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

• Model Prediction of Absence/Presence of OSA: Passive Collapsibility

  Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. The passive collapsibility of the upper airway is quantified as the ventilation on no CPAP (atmospheric pressure) at the eupneic level of ventilatory drive when upper airway dilator muscles are relatively passive. This trait is symbolized as Vpassive (L/min)

  Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

• Model Prediction of Absence/Presence of OSA: Active Collapsibility (Vactive)

  Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence. Active collapsibility is the ventilation on no CPAP when upper airway muscle are maximally activated. It is calculated by slowing reducing CPAP from the optimal to the minimum tolerable level and rapidly dropping the CPAP to 0 for a few breaths. This trait is symbolized as Vactive (L/min)

  Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Secondary Outcomes (1)

• Apnea-Hypopnea Index

  Subjects will be assessed on day 1 (visit 1) and up to 1 month (visit 2)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects will receive both a sugar pill and room air during their overnight sleep studies

Drug: Placebo pill; Other: Room air

Treatment

ACTIVE COMPARATOR

Subjects will receive both Lunesta (eszopiclone) and medical grade oxygen during their overnight sleep studies

Drug: Sedative; Other: Oxygen

Interventions

Placebo pill DRUG

Subjects will receive a sugar pill (in combination with room air) during their placebo arm studies

Also known as: sugar pill

Placebo

Sedative DRUG

Subjects will receive eszopiclone (in combination with medical oxygen) during their treatment arm studies

Also known as: Lunesta

Treatment

Room air OTHER

Subjects will receive room air (in combination with a sugar pill) during their placebo arm studies

Placebo

Oxygen OTHER

Subjects will receive medical grade oxygen (in combination with eszopiclone) during their treatment arm studies

Treatment

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 - 79 years
• Documented OSA (AHI \> 10 events/hr Non rapid eye movement sleep supine)
• If treated then, current CPAP use (\>4 hrs CPAP/night for \> 2 months)

You may not qualify if:

• Any uncontrolled medical condition
• Any other sleep disorder (Periodic leg movement syndrome, restless legs syndrome, insomnia, etc.)
• Use of medications known to affect sleep/arousal, breathing, or muscle physiology
• Allergy to lidocaine or Afrin
• Claustrophobia
• Alcohol consumption within 24 hours of PSG

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (2)

• Landry SA, Joosten SA, Sands SA, White DP, Malhotra A, Wellman A, Hamilton GS, Edwards BA. Response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient's therapeutic CPAP requirement. Respirology. 2017 Aug;22(6):1219-1224. doi: 10.1111/resp.13044. Epub 2017 Apr 13.

  PMID: 28409851 DERIVED

• Edwards BA, Sands SA, Owens RL, Eckert DJ, Landry S, White DP, Malhotra A, Wellman A. The Combination of Supplemental Oxygen and a Hypnotic Markedly Improves Obstructive Sleep Apnea in Patients with a Mild to Moderate Upper Airway Collapsibility. Sleep. 2016 Nov 1;39(11):1973-1983. doi: 10.5665/sleep.6226.

  PMID: 27634790 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Sugars; Hypnotics and Sedatives; Eszopiclone; Oxygen

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Carbohydrates; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Pyridines; Chalcogens; Elements; Inorganic Chemicals; Gases

Limitations and Caveats

The overall limitation is that we have only assessed the impact of combination therapy on one night. Thus, longitudinal studies will be needed to determine if the treatments remain effective.

Results Point of Contact

• Title: David Andrew Wellman
• Organization: Brigham and Women's Hospital

awellman@rics.bwh.harvard.edu

617-732-8483

Study Officials

• David A Wellman, MD

  Brigham & Womens Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 25, 2012
• First Posted: July 4, 2012
• Study Start: August 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 3, 2017
• Results First Posted: March 3, 2017

Record last verified: 2017-01

Locations

US (1)