NCT03736382

Brief Summary

Mild intermittent hypoxia (IH) initiates sustained increases in chest wall and upper airway muscle activity in humans. This sustained increase is a form of respiratory plasticity known as long-term facilitation (LTF). Repeated daily exposure to mild IH that leads to the initiation of LTF of upper airway muscle activity could lead to increased stability of the upper airway. In line with PI's laboratory's mandate to develop innovative therapies to treat sleep apnea, this increased stability could ultimately reduce the continuous positive airway pressure (CPAP) required to treat obstructive sleep apnea (OSA) and improve compliance with this gold standard treatment. Improved compliance could ultimately serve to mitigate those comorbidities linked to sleep apnea. Moreover, in addition to improving CPAP compliance numerous studies indicate that mild IH has many direct beneficial effects on cardiovascular, neurocognitive and metabolic function. Thus, mild IH could serve as a multipronged therapeutic approach to treat sleep apnea. In accordance with this postulation, our proposal will determine if repeated daily exposure to mild IH serves as an adjunct therapy coupled with CPAP to mitigate associated co-morbidities via its direct effects on a variety of cardiovascular, metabolic and neurocognitive measures and indirectly by improving CPAP compliance. Modifications in autonomic (i.e. sympathetic nervous system activity) and cardiovascular (i.e. blood pressure) function will be the primary outcome measures coupled to secondary measures of metabolic and neurocognitive outcomes.

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Nov 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 2, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 9, 2018

Completed
6 days until next milestone

Study Start

First participant enrolled

November 15, 2018

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2025

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2025

Completed
Last Updated

July 19, 2024

Status Verified

July 1, 2024

Enrollment Period

6.6 years

First QC Date

November 2, 2018

Last Update Submit

July 18, 2024

Conditions

Obstructive Sleep ApneaSpinal Cord Injuries

Keywords

Mild Intermittent HypoxiaContinuous positive airway pressure therapy

Outcome Measures

Primary Outcomes (1)

  • Change in blood pressure measured during quiet wakefulness over the 24 hour period following mild intermittent hypoxia and sham protocol

    24 hour blood pressure measures will be obtained prior to the beginning and at the end of protocol to quantify blood pressure changes following mild intermittent hypoxia.

    Before and after 15 days of exposure to mild intermittent hypoxia or a sham protocol.

Secondary Outcomes (13)

  • Change in blood pressure measured during sleep over 24 hours following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in beat to beat measures of blood pressure following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in sympathetic and parasympathetic nervous system activity following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in learning and memory following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in attention following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • +8 more secondary outcomes

Other Outcomes (3)

  • Change in upper airway collapsibility following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in therapeutic pressure following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

  • Change in CPAP treatment adherence following mild intermittent hypoxia and sham protocol

    Day 1 and Day 15 of the protocol

Study Arms (2)

Experimental Group

EXPERIMENTAL

The experimental group is comprised of participants with OSA and hypertension \[either able bodied (Aim 1) or with spinal cord injury (Aim 2)\] that will be treated with mild IH and CPAP. In the present proposal, the mild IH protocol will be administered during wakefulness each day for 15 days over a 3-week period to participants that will also be treated with CPAP during sleep. The mild IH protocol will be comprised of a 20-minute baseline period followed by exposure to twelve - two minute episodes of hypoxia \[partial pressure of end-tidal oxygen (PETO2) = 50 mmHg\]. Each episode will be interspersed with a 2-minute recovery period under normoxic conditions. The PETCO2 will be sustained 2 mmHg above baseline values for the last ten minutes of baseline and throughout the remainder of the protocol.

Other: Mild intermittent hypoxiaOther: Continuous positive airway pressure (CPAP)

Control Group

SHAM COMPARATOR

The control group is comprised of hypertensive OSA participants \[either able bodied (Aim 1) or with spinal cord injury (Aim 2)\] that will be exposed to a sham protocol in addition to being treated with CPAP during sleep. The sham protocol will be administered during wakefulness for 15 days over a 3-week period. During the sham protocol the participants will be exposed to atmospheric levels of oxygen and carbon dioxide for the duration of the protocol.

Other: Sham protocolOther: Continuous positive airway pressure (CPAP)

Interventions

Mild intermittent hypoxiaOTHER

Participants will be exposed to twelve two minute episodes of mild intermittent hypoxia 5 days a week for 3 weeks.

Experimental Group
Sham protocolOTHER

Participants will be exposed to twelve two minute episodes of sham mild intermittent hypoxia (i.e. room air) 5 days a week for 3 weeks.

Control Group
Continuous positive airway pressure (CPAP)OTHER

All participants will be treated with CPAP each night for a duration of 3 weeks.

Control GroupExperimental Group

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Body mass index \< 40 kg/m\^2.
  • to 60 years old.
  • Newly diagnosed sleep apnea (i.e. apnea/hypopnea index \< 100 events per hour - average nocturnal oxygen saturation \> 85 %) that has not been treated.
  • Diagnosed with prehypertension or Stage 1 hypertension as categorized by the American Heart Association
  • Not pregnant.
  • Normal lung function.
  • Minimal alcohol consumption (i.e. no more than the equivalent of a glass of wine/day)
  • A typical sleep/wake schedule (i.e. participants will not be night shift workers or have recently travelled across time zones).
  • For spinal cord injured participants (Aim-2): incomplete spinal cord lesions at C3 or below and above T12 (greater than 36 mos. post-SCI) without joint contractures but with signs of voluntary ankle, knee and hip movements and the ability to ambulate at least one step without human assistance.

You may not qualify if:

  • Any disease other than high blood pressure and sleep apnea.
  • Medications for high blood pressure and sleep promoting supplements including melatonin
  • Current effective CPAP usage (greater than 4 hours per night).
  • Night Shift workers or recently traveled across time zones.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

John D Dingell VA Medical Center

Detroit, Michigan, 48201, United States

RECRUITING

Wayne State University

Detroit, Michigan, 48201, United States

RECRUITING

Related Publications (1)

  • Panza GS, Puri S, Lin HS, Badr MS, Mateika JH. Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male Patients with Obstructive Sleep Apnea and Hypertension. Am J Respir Crit Care Med. 2022 Apr 15;205(8):949-958. doi: 10.1164/rccm.202108-1808OC.

    PMID: 35015980DERIVED

MeSH Terms

Conditions

Sleep Apnea, ObstructiveSpinal Cord Injuries

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Sleep Apnea SyndromesApneaRespiration DisordersRespiratory Tract DiseasesSleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System DiseasesSpinal Cord DiseasesCentral Nervous System DiseasesTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

Positive-Pressure RespirationRespiration, ArtificialAirway ManagementTherapeuticsRespiratory Therapy

Study Officials

  • Jason H Mateika, Ph.D.

    Wayne State University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason H Mateika, Ph.D.

CONTACT

313-576-4481am1819@wayne.edu

Shipra Puri, Ph.D.

CONTACT

313-576-4414shiprapuri@wayne.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

November 2, 2018

First Posted

November 9, 2018

Study Start

November 15, 2018

Primary Completion

June 30, 2025

Study Completion

November 30, 2025

Last Updated

July 19, 2024

Record last verified: 2024-07

Data Sharing

IPD Sharing
Will not share

Publication in peer-reviewed biomedical literature will be the principal means by which final data will be shared. All published papers will be deposited in PubMed Central archive no later than 1 year after publication. When possible, appropriate, and supported by publisher, PI will consider making de-identified data sets available as supplemental material for published manuscripts. Data sets will be uncensored and described in sufficient detail so that others will be able to independently perform statistical analyses to support (or challenge) our conclusions, as well as apply different analytical methods that may give rise to new conclusions and generate new hypotheses. Preservation and access to final data sets will be maintained locally until enterprise-level resources become available for long-term storage and access. Data will be maintained electronically behind secure Wayne State University firewall. This data will also be kept for six years following the close of study protocol.

Locations

US(2)