Sleep Disordered Breathing and Chronic Pain

BiPAP Adaptive Servo-Ventilation (AutoSV) Therapy in Patients With Chronic Pain and Sleep Disordered Breathing (SDB)

The purpose of this study is to evaluate positive pressure in patients with chronic pain taking opioid medications who have sleep disordered breathing.

Study Overview

• Status: Completed
• Conditions: Sleep Apnea Syndromes
• Intervention / Treatment: Device: servo ventilation auto; Device: Continuous positive airway pressure; Device: servo ventilation manual

Detailed Description

Purpose: Opioid treatment of non-malignant chronic pain can result in hypoxemia, hypercarbia, and central sleep apnea. The aim of this study was to determine the initial efficacy of auto servo-ventilation (ASV) and after 3 months of home use.

Methods: This prospective multicenter interventional study recruited chronic pain patients prescribed ≥100 morphine equivalents for at least 4 months.

Participants: Following full-night polysomnography (PSG) to confirm the presence of sleep-disordered breathing, patients were randomized to three additional full-night-attended PSGs with continuous positive airway pressure (CPAP), ASV, and servo-ventilation with an initial mandatory pressure support of 6 cm water (H2O) ASV manual Minimum Pressure Support (PSmin). Following the PSGs, patients were sent home with EncoreAnywhere and ASV with or without mandatory pressure support.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Sleep D/O Center of Alabama
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Arkansas Center for Sleep Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research Inc.
  • Missouri
    • St. Louis, Missouri, United States, 63143
      • Clayton Sleep Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females, ages 21-70.
2. Able to provide written informed consent.
3. Diagnosis of chronic non-malignant pain (pain present for ≥ 6 months).
4. Stable regimen of opioids (oral, transdermal, and/or intravenous) for chronic pain for at least 4 weeks prior to study participation with a prescribed opioid dose equal to at least 100 milliequivalents of morphine per 24 hours (Appendix 1).
5. Agreement to undergo an in-lab Diagnostic polysomnography (PSG) demonstrating an Apnea-Hypopnea Index (AHI) of at least 20 and Central Apnea Index (CAI) ≥ 10 events per hour of sleep OR at least 25% of Total Sleep Time (TST) below 90% Oxygen Saturation (SAO2) saturation and AHI ≥ 10
6. Agreement to undergo 3 full-night, in-lab PSG's on positive airway pressure therapy.
7. Agreement to undergo breathalyzer testing prior to each PSG visit
8. Ability to provide reliable documentation of opioid medications (ex. Pharmacy records) as treatment for chronic pain for the previous 30 days.
9. Willingness to undergo urine drug screening.

Exclusion Criteria:

1. Participation in other interventional, sleep or pharmaceutical related research studies within 30 days prior to giving consent.
2. Workers with variable shift schedules.
3. Previous treatment with positive airway pressure therapy within 90 days of providing consent.
4. Participants with any conditions in which positive airway pressure is medically contraindicated (e.g. recent pneumothorax, systolic BP < 80 mmHg).
5. BMI > 40
6. Unwilling to wear PAP.
7. Any surgery involving the upper airway, eye, nose, sinuses or middle ear within the last 90 days.
8. Major or poorly managed medical or psychiatric condition that would interfere with the demands of the study, to the use of positive airway pressure, or the ability to complete the study.
9. Previous diagnosis of severe chronic obstructive pulmonary disease (COPD) with an forced expiratory volume at one second (FEV1) < 1 liter or less than 50% predicted
10. Presence of elevated arterial carbon dioxide levels while awake (PaCO2 ≥ 50mmHg) due to intrinsic lung disease, neuromuscular or musculoskeletal disorders.
11. Participants currently prescribed 24 hour oxygen therapy (nocturnal O2 therapy for obstructive sleep apnea (OSA) treatment is allowed)
12. Females who are pregnant or, if of child bearing potential, not currently using medically reliable birth control methods.
13. Participants prescribed opioids for reasons other than the management of chronic, non-malignant pain.
14. Failure of two consecutive breathalyzer tests from study PSG nights
15. Periodic Limb Movements (PLM's) with arousals > 15

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: servo ventilation auto mode; Inspiratory and expiratory pressures automatically determined by the servo ventilation device.	Device: servo ventilation auto; Expiratory pressure automatically adjusted to stabilize the upper airway. Inspiratory pressure automatically adjusted to deliver consistent peak flow.; Device: Continuous positive airway pressure; continuous positive airway pressure; Other Names: CPAP; Device: servo ventilation manual; servo ventilation titrated in manual mode
Active Comparator: Continuous positive airway pressure; Airway pressure delivered at a constant pressure level.	Device: Continuous positive airway pressure; continuous positive airway pressure; Other Names: CPAP; Device: servo ventilation manual; servo ventilation titrated in manual mode
Active Comparator: servo ventilation manual; Inspiratory and expiratory pressures automatically determined by the servo ventilation device with mandatory minimal inspiratory minus expiratory pressure difference.	Device: servo ventilation manual; servo ventilation titrated in manual mode

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Sleep Related Events Per Hour	The number of Apnea-Hypopnea Events, Central Apneas, Obstructive Apneas and Hypopneas were compared among no treatment, CPAP, Auto SV and Manual SV.	four full night Polysomnography (PSG's)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Oxygen Saturation	Oxygen Saturation were compared among using no treatment, CPAP, Auto SV and Manual SV.	four full night Polysomnography (PSG's)
Number of Arterial Oxygen Saturation Per Hour	Arterial Oxygen Saturation was compared among using no treatment, CPAP, Auto SV and Manual SV.	four full night Polysomnography (PSG's)

Collaborators and Investigators

• Sponsor: Philips Respironics
• Investigators: Principal Investigator: Mark Muehlbach, PhD, Clayton Sleep Institute; Principal Investigator: Paul Wylie, MD, Arkansas Center of Sleep Medicine; Principal Investigator: Vernon Pegram, PhD, Sleep D/O Center of Alabama; Principal Investigator: Russell Rosenberg, MD, NeuroTrials Research, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 20, 2011
• First Posted (Estimate): October 21, 2011

Study Record Updates

• Last Update Posted (Estimate): February 19, 2016
• Last Update Submitted That Met QC Criteria: January 22, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: chronic pain; Opioids; sleep disordered breathing
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pain; Neurologic Manifestations; Sleep Apnea Syndromes; Chronic Pain
• Other Study ID Numbers: SDBPM-2011-01