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Mild Intermittent Hypoxia and Its Multipronged Effect on Sleep Apnea

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ClinicalTrials.gov Identifier: NCT03736382
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : October 9, 2019
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jason H Mateika, Wayne State University

Brief Summary:
Mild intermittent hypoxia (MIH) 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.

Condition or disease Intervention/treatment Phase
Obstructive Sleep Apnea Other: Mild intermittent hypoxia Other: Sham protocol Other: Continuous positive airway pressure (CPAP) Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Mild Intermittent Hypoxia and CPAP: A Multi-pronged Approach to Treat Sleep Apnea in Intact and Spinal Cord Injured Humans
Actual Study Start Date : November 15, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Experimental: Hypoxia Group
The hypoxia group is comprised of participants with OSA and hypertension that will be treated with IH and CPAP. In the present proposal, the 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 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 hypoxia
Participants will be exposed to twelve two minute episodes of mild intermittent hypoxia 5 days a week for 3 weeks.

Other: Continuous positive airway pressure (CPAP)
All participants will be treated with CPAP each night for a duration of 3 weeks.

Sham Comparator: Sham Group
The sham group will be comprised of hypertensive OSA participants 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 a minimum of 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 IH protocol.
Other: Sham protocol
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.

Other: Continuous positive airway pressure (CPAP)
All participants will be treated with CPAP each night for a duration of 3 weeks.




Primary Outcome Measures :
  1. Change in 24 hour systolic, diastolic and mean arterial blood pressure following mild intermittent hypoxia+ CPAP therapy [ Time Frame: Before and after 15 days of exposure to mild intermittent hypoxia or a sham protocol. ]
    24 hour systolic, diastolic and mean arterial 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.

  2. Change in beat to beat measures of systolic and diastolic blood pressure following mild intermittent hypoxia+ CPAP therapy [ Time Frame: Day 1, Day 8 and Day 15 of the protocol ]
    Beat to beat blood pressure measures will be obtained prior to the administration of mild intermittent hypoxia or sham protocol on Day 1, Day 8 and Day 15 of the study protocol to quantify changes induced by MIH+CPAP therapy on beat to beat blood pressure.

  3. Change in sympathetic and parasympathetic nervous system activity following mild intermittent hypoxia+ CPAP therapy [ Time Frame: Day 1, Day 8 and Day 15 of the protocol ]
    Beat to beat blood pressure and electro cardiogram recordings will be obtained to quantify changes in sympathetic and para sympathetic activities due to MIH+CPAP therapy


Secondary Outcome Measures :
  1. Change in learning and memory following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1 and Day 15 of the protocol ]
    The Buschke Selective Reminding Test will be used to assess changes in learning and memory following mild intermittent hypoxia or sham protocol

  2. Change in attention following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1 and Day 15 of the protocol ]
    The Pathfinder Number Test will assess changes in attention following mild intermittent hypoxia or sham protocol

  3. Change in psychomotor function following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1 and Day 15 of the protocol ]
    Psychomotor Vigilance Task will be used to measure changes in psychomotor function following mild intermittent hypoxia or sham protocol

  4. Change in daytime sleepiness following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1 and Day 15 of the protocol ]
    The Epworth Sleepiness Scale will assess day time sleepiness in mild intermittent hypoxia or sham groups.

  5. Change in overall cognitive function following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1 and Day 15 of the protocol ]
    The Mini Mental State Examination will be used to assess five areas of cognition function (i.e. orientation, registration, attention, calculation, recall and language) in mild intermittent hypoxia or sham groups.


Other Outcome Measures:
  1. Change in metabolic biomarkers following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1, Day 8 and Day 15 of the protocol ]
    Change in lipid profile and hemoglobin A1C will be used to assess the changes in metabolic biomarkers following mild intermittent hypoxia or sham protocol

  2. Change in inflammatory biomarkers following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1, Day 8 and Day 15 of the protocol ]
    Change in inflammatory biomarkers will be assessed from asymmetric dimethylarginine and high sensitivity C-reactive protein.

  3. Change in angiogenic/vasculogenic biomarkers following mild intermittent hypoxia + CPAP therapy [ Time Frame: Day 1, Day 8 and Day 15 of the protocol ]
    Change in hypoxia inducible factor 1α and vascular endothelial growth factor will be used to quantify changes in angiogenic/vasculogenic biomarkers.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body mass index < 40 kg/m^2.
  • 18 to 60 years old.
  • Newly diagnosed sleep apnea (i.e. apnea/hypopnea index < 80 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).

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03736382


Contacts
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Contact: Jason H Mateika, Ph.D. 313-576-4481 am1819@wayne.edu
Contact: Shipra Puri, Ph.D. 313-576-4454 shiprapuri@wayne.edu

Locations
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United States, Michigan
John D Dingell VA Medical Center Recruiting
Detroit, Michigan, United States, 48201
Contact: Jason H Mateika, Ph.D.    313-576-4481    am1819@wayne.edu   
Contact: Shipra Puri, Ph.D.    313-576-4454    shiprapuri@wayne.edu   
Principal Investigator: Jason H Mateika, Ph.D.         
Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Jason H Mateika, Ph.D.    313-576-4481    am1819@wayne.edu   
Contact: Shipra Puri, Ph.D.    313-576-4454    shiprapuri@wayne.edu   
Principal Investigator: Jason H Mateika, Ph.D.         
Sponsors and Collaborators
Wayne State University
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Jason H Mateika, Ph.D. Wayne State University
  Study Documents (Full-Text)

Documents provided by Jason H Mateika, Wayne State University:

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Responsible Party: Jason H Mateika, Principal Investigator, Wayne State University
ClinicalTrials.gov Identifier: NCT03736382     History of Changes
Other Study ID Numbers: 1R56HL142757-01 ( U.S. NIH Grant/Contract )
1R56HL142757-01 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2018    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jason H Mateika, Wayne State University:
Mild Intermittent hypoxia
Continuous positive airway pressure therapy
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Hypoxia
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Dyssomnias
Nervous System Diseases
Cytarabine
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors