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Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea

Primary Purpose

Sleep Apnea

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
PAP
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Sleep Apnea focused on measuring Sleep apnea, Hypoxic burden, Arousal intensity, Post-event tachycardia, Positive airway pressure, Apnea hypopnea index

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Adults aged 21-80 years.
  • Participants with a previous diagnosis of moderate to severe obstructive sleep will be eligible to enroll and attend the baseline study. Patients with a total apnea-hypopnea index greater than 15 events/hr on the baseline study will be eligible for further participation.

Exclusion criteria:

  • Current treatment for obstructive sleep apnea (including CPAP, oral appliances, supplemental oxygen). Patients must be untreated prior to the baseline visit.
  • Use of medications that might depress respiration (including opioids, barbiturates, benzodiazepines, and Z drugs, including zolpidem, zopiclone, eszopiclone, and zaleplon).
  • Active use of non-prescription opioids (e.g., cocaine, methamphetamine)
  • Uncontrolled medical problem or major organ system disease, which, in the opinion of the investigators (PI and Co-Is), would interfere with the evaluation of the subject (e.g., uncontrolled hypertension, unstable coronary heart disease, etc.).
  • History of congestive heart failure, renal insufficiency, systemic neurological condition that could affect respiration.

  • Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:

    • central sleep apnea (>50% of respiratory events scored as central),
    • chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions.
  • Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
  • Patients unable or unwilling to use CPAP.
  • Insomnia or insufficient sleep (self-reported inability to sleep >6 hrs night).
  • Pregnancy (women)

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Positive Airway Pressure Device

Arm Description

All participants will receive PAP therapy

Outcomes

Primary Outcome Measures

Change from baseline flow-mediated vasodilation at 12 weeks
Flow mediated vasodilation is studied using high resolution ultrasound of the artery.
Change from baseline 24-hour mean systolic blood pressure at 12 weeks
Mean systolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Change from baseline Epworth Sleepiness Scale (ESS) at 12 weeks
Self-reported sleepiness measured using the Epworth Sleepiness Scale (units on a scale). Values range from 0-24; higher values indicate greater sleepiness.

Secondary Outcome Measures

Change from baseline F2-Isoprostane/Creatinine Ratio at 12 weeks
F2-Isoprostane/Creatinine Ratio, a measure of oxidative stress, is calculated from urine sample.
Change from baseline Albumin/Creatinine Ratio at 12 weeks
Urinary Albumin/Creatinine Ratio is calculated from urine samples.
Change from baseline Albumin without Creatinine at 12 weeks
Urinary Albumin is calculated from urine samples.
Change from baseline Oxidized low-density lipoprotein (LDL) at 12 weeks
Oxidized low-density lipoprotein measurements are calculated through fasting phlebotomy.
Change from baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks
N-terminal pro b-type natriuretic peptide (NT-proBNP) measurements are calculated through fasting phlebotomy.
Change from baseline Hemoglobin A1c (HbA1c) at 12 weeks
Hemoglobin A1c (HbA1c) measurements are calculated through fasting phlebotomy.
Change from baseline Plasminogen Activator Inhibitor-1 at 12 weeks
Plasminogen activator inhibitor type 1 (PAI-1) measurements are calculated through fasting phlebotomy.
Change from baseline Fibrinogen Antigen at 12 weeks
Fibrinogen Antigen measurements are calculated through fasting phlebotomy. High values indicate inflammation and increased risk of atherosclerosis.
Change from baseline Glucose at 12 weeks
Blood glucose measurements are calculated through fasting phlebotomy
Change from baseline high sensitivity C-Reactive Protein (hs-CRP) at 12 weeks
C-reactive protein measurements are calculated from blood samples collected through fasting phlebotomy.
Change from baseline Interleukin-6 (IL-6) at 12 weeks
IL-6 is calculated from blood samples collected through fasting phlebotomy
Change from baseline Creatinine at 12 weeks
Creatinine is calculated from blood samples collected through fasting phlebotomy
Change from baseline Cystanin C with eGFR at 12 weeks
Cystanin C with eGFR is calculated from blood samples collected through fasting phlebotomy
Change from baseline lipid panel at 12 weeks
Lipid panel measurements are calculated from blood samples collected through fasting phlebotomy.
Change from baseline 24-hour mean diastolic blood pressure at 12 weeks
Mean diastolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Change from baseline 24-hour mean blood pressure at 12 weeks
Mean arterial blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Change from baseline nocturnal mean systolic blood pressure at 12 weeks
Mean systolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Change from baseline nocturnal mean diastolic blood pressure at 12 weeks
Mean diastolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Change from baseline nocturnal mean blood pressure at 12 weeks
Mean arterial blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Change from baseline Psychomotor Vigilance Task reaction time at 12 weeks
3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.
Change from baseline Psychomotor Vigilance Task lapses per test at 12 weeks
3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.
Change from baseline Functional Outcome of Sleep Questionnaire (FOSQ) at 12 weeks
This test will be used to assess the impact of excessive sleepiness on functional outcomes relevant to daily behaviors and sleep-related quality of life.

Full Information

First Posted
September 16, 2020
Last Updated
December 13, 2021
Sponsor
Brigham and Women's Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT04575740
Brief Title
Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea
Official Title
Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
September 10, 2020 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes

5. Study Description

Brief Summary
Obstructive sleep apnea (OSA) is a highly prevalent disorder with adverse neurocognitive and cardio-metabolic outcomes. Continuous positive airway pressure (CPAP) is the gold standard therapeutic option to treat airway obstructions during sleep and thus, prevent its adverse cardiovascular and neurocognitive outcomes. Previous clinical trials, however, have largely failed to show a consistent impact of CPAP on these health outcomes. One of the main limitations of these trials may be the inadequate characterization of OSA and its acute physiological consequences. By characterizing OSA based on the "apnea-hypopnea index (AHI)", there is a potential risk of negative results. In this trial, the investigators intend to tackle this issue, by better characterization of OSA-related physiological consequences during sleep using physiologically driven metrics to capture the burden of OSA-related hypoxemia ("hypoxic burden"), autonomic response ("heart rate burden"), and sleep fragmentation ("arousal burden").

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea
Keywords
Sleep apnea, Hypoxic burden, Arousal intensity, Post-event tachycardia, Positive airway pressure, Apnea hypopnea index

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
158 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Positive Airway Pressure Device
Arm Type
Experimental
Arm Description
All participants will receive PAP therapy
Intervention Type
Device
Intervention Name(s)
PAP
Intervention Description
Positive airway pressure to treat sleep apnea
Primary Outcome Measure Information:
Title
Change from baseline flow-mediated vasodilation at 12 weeks
Description
Flow mediated vasodilation is studied using high resolution ultrasound of the artery.
Time Frame
12 weeks
Title
Change from baseline 24-hour mean systolic blood pressure at 12 weeks
Description
Mean systolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline Epworth Sleepiness Scale (ESS) at 12 weeks
Description
Self-reported sleepiness measured using the Epworth Sleepiness Scale (units on a scale). Values range from 0-24; higher values indicate greater sleepiness.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change from baseline F2-Isoprostane/Creatinine Ratio at 12 weeks
Description
F2-Isoprostane/Creatinine Ratio, a measure of oxidative stress, is calculated from urine sample.
Time Frame
12 weeks
Title
Change from baseline Albumin/Creatinine Ratio at 12 weeks
Description
Urinary Albumin/Creatinine Ratio is calculated from urine samples.
Time Frame
12 weeks
Title
Change from baseline Albumin without Creatinine at 12 weeks
Description
Urinary Albumin is calculated from urine samples.
Time Frame
12 weeks
Title
Change from baseline Oxidized low-density lipoprotein (LDL) at 12 weeks
Description
Oxidized low-density lipoprotein measurements are calculated through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline N-terminal pro b-type natriuretic peptide (NT-proBNP) at 12 weeks
Description
N-terminal pro b-type natriuretic peptide (NT-proBNP) measurements are calculated through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline Hemoglobin A1c (HbA1c) at 12 weeks
Description
Hemoglobin A1c (HbA1c) measurements are calculated through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline Plasminogen Activator Inhibitor-1 at 12 weeks
Description
Plasminogen activator inhibitor type 1 (PAI-1) measurements are calculated through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline Fibrinogen Antigen at 12 weeks
Description
Fibrinogen Antigen measurements are calculated through fasting phlebotomy. High values indicate inflammation and increased risk of atherosclerosis.
Time Frame
12 weeks
Title
Change from baseline Glucose at 12 weeks
Description
Blood glucose measurements are calculated through fasting phlebotomy
Time Frame
12 weeks
Title
Change from baseline high sensitivity C-Reactive Protein (hs-CRP) at 12 weeks
Description
C-reactive protein measurements are calculated from blood samples collected through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline Interleukin-6 (IL-6) at 12 weeks
Description
IL-6 is calculated from blood samples collected through fasting phlebotomy
Time Frame
12 weeks
Title
Change from baseline Creatinine at 12 weeks
Description
Creatinine is calculated from blood samples collected through fasting phlebotomy
Time Frame
12 weeks
Title
Change from baseline Cystanin C with eGFR at 12 weeks
Description
Cystanin C with eGFR is calculated from blood samples collected through fasting phlebotomy
Time Frame
12 weeks
Title
Change from baseline lipid panel at 12 weeks
Description
Lipid panel measurements are calculated from blood samples collected through fasting phlebotomy.
Time Frame
12 weeks
Title
Change from baseline 24-hour mean diastolic blood pressure at 12 weeks
Description
Mean diastolic blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline 24-hour mean blood pressure at 12 weeks
Description
Mean arterial blood pressure over a 24-hour period is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline nocturnal mean systolic blood pressure at 12 weeks
Description
Mean systolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline nocturnal mean diastolic blood pressure at 12 weeks
Description
Mean diastolic blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline nocturnal mean blood pressure at 12 weeks
Description
Mean arterial blood pressure during sleep is measured using an ambulatory blood pressure monitor.
Time Frame
12 weeks
Title
Change from baseline Psychomotor Vigilance Task reaction time at 12 weeks
Description
3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.
Time Frame
12 weeks
Title
Change from baseline Psychomotor Vigilance Task lapses per test at 12 weeks
Description
3-minute Psychomotor Vigilance Tasks will be done to quantify the speed with which subjects respond to a visual stimulus.
Time Frame
12 weeks
Title
Change from baseline Functional Outcome of Sleep Questionnaire (FOSQ) at 12 weeks
Description
This test will be used to assess the impact of excessive sleepiness on functional outcomes relevant to daily behaviors and sleep-related quality of life.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Adults aged 21-80 years. Participants with a previous diagnosis of moderate to severe obstructive sleep will be eligible to enroll and attend the baseline study. Patients with a total apnea-hypopnea index greater than 15 events/hr on the baseline study will be eligible for further participation. Exclusion criteria: Current treatment for obstructive sleep apnea (including CPAP, oral appliances, supplemental oxygen). Patients must be untreated prior to the baseline visit. Use of medications that might depress respiration (including opioids, barbiturates, benzodiazepines, and Z drugs, including zolpidem, zopiclone, eszopiclone, and zaleplon). Active use of non-prescription opioids (e.g., cocaine, methamphetamine) Uncontrolled medical problem or major organ system disease, which, in the opinion of the investigators (PI and Co-Is), would interfere with the evaluation of the subject (e.g., uncontrolled hypertension, unstable coronary heart disease, etc.). History of congestive heart failure, renal insufficiency, systemic neurological condition that could affect respiration. Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea: central sleep apnea (>50% of respiratory events scored as central), chronic hypoventilation/hypoxemia (awake SaO2 < 92% by oximetry) due to chronic obstructive pulmonary disease or other respiratory conditions. Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias. Patients unable or unwilling to use CPAP. Insomnia or insufficient sleep (self-reported inability to sleep >6 hrs night). Pregnancy (women)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nkiru G Ujomu
Phone
617-732-8976
Email
nujomu@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kiley E Blodgett
Phone
617-732-8976
Email
keblodgett@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ali Azarbarzin, PhD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nkiru G Ujomu
Phone
617-732-8976
Email
nujomu@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Kiley Blodgett
Email
keblodgett@bwh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes

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Phenotyping Mechanistic Pathways for Adverse Health Outcomes in Sleep Apnea

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