Sleep Disordered Breathing and Cardiopulmonary Disease in Peruvian Highlanders

Overall objective: To understand the feasibility of performing a randomized trial using a simple, minimally-invasive postural therapy approach to improve sleep disordered breathing (SDB).

Study Overview

• Status: Completed
• Conditions: Sleep Apnea; Sleep Disordered Breathing
• Intervention / Treatment: Device: Inclined Sleep

Detailed Description

Specific Aims:

• To examine the relative efficacy of postural therapy (a 15-degree wedge mattress) on measures of chronic cardiometabolic stress in high altitude residents.
• To determine the tolerability of postural therapy.

Primary outcomes, at 4 and 8 weeks:

• Mean nocturnal oxyhemoglobin saturation (SPO2)
• Apnea-hypopnea index (AHI).

Secondary outcomes

• Markers of hypoxemia exposure: the investigators will evaluate for differences in average hemoglobin and erythropoietin concentrations between intervention groups using t-tests or Wilcoxon rank sum tests, as considered appropriate. If transformations are necessary, the investigators will use Box-Cox power transform to identify the best transformation for the investigators' data.
• Markers of metabolic dysfunction: the investigators will evaluate for differences in average Glycated hemoglobin test (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL), High-density lipoprotein cholesterol (HDL), triglycerides, SVEGF-R1 , and soluble Vascular Endothelial Growth Factor (SVEGF-1) concentrations between intervention groups using t-tests or Wilcoxon rank sum tests, as appropriate. If transformations are necessary, the investigators will use Box-Cox power transform to identify the best transformation for the investigators' data.
• Markers of cardiometabolic stress: the investigators will evaluate for differences in average systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse, and % change in endothelial function (reactive hyperemia index) as assessed by brachial artery reactivity testing (BART) between intervention groups using t-tests or Wilcoxon rank sum tests, as considered appropriate.
• Adherence (the average number of nights during the 8-week period that participants slept on the wedge mattress),

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Peru
  • Puno, Peru
    • Prisma Org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria

• Age 40-80 years
• Daytime oxyhemoglobin saturation ≥80%, seated.
• Body mass index ≥25 kg/m2
• Hemoglobin >13 g/dL in women and >15 g/dL in men
• Ability to provide informed consent
• Sleeps at home in same bed every night
• Expected stable residence for at least 6 months
• Sleeps with two pillows or fewer
• Demonstrate acute improvement in SDB severity with postural therapy
• Able to sleep ≥5 hours at an incline for all three nights during the run-in period

Exclusion criteria

• Works the night-shift or a rotating shift
• Has an indication or preference for sleeping upright, semi-recumbent or at an incline
• Chronic insomnia or a non-respiratory sleep disorder
• Physician-established diagnosis of diabetes, lung, cardiovascular, liver, or chronic kidney disease
• Using home oxygen therapy or other respiratory assistive device [e.g., continuous positive airway pressure (CPAP), nebulizer]
• Self-reported severe gastrointestinal reflux
• Self-report of occult blood or history of gastrointestinal bleeding in the past 3 months
• Pregnancy
• Unable to sleep ≥5 hours at an incline for all three nights during the run-in period

The following exclusion criteria apply only for those undergoing spirometry for safety reasons. Participants with any one of these criteria, will be excluded from spirometry but can still participate in the rest of the screening phase:

• Surgery of the heart, chest, lungs in the past 3 months (participants will be revisited at a later period)
• Heart attack in the past 3 months (participants will be revisited at a later period)
• History of eye surgery
• History of abdominal surgery in the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Inclined Sleep; Inclined mattress at 15 degrees	Device: Inclined Sleep; Study participants randomized to the interventional arm will be instructed to sleep on inclined wedge mattress.; Other Names: wedge mattress; postural therapy
NO_INTERVENTION: Flat Sleep; Plane mattress

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Respiratory Disturbance Index (RDI)	The investigators will measure a change in Respiratory Disturbance Index (RDI) defined as an oxygen desaturation of at least 4 percent associated with autonomic signs of arousal. Specifically, autonomic arousals are defined as concurrent rises in heart rate and attenuation of arterial tonometry. Normal < 5 percent 5 percent < Mild < 15 percent 15 percent < Moderate < 30 percent Severe > 30 percent	Baseline, 4 weeks, 8 weeks
Change in Mean oxyhemoglobin saturation (percent) during sleep	The investigators will measure mean oxyhemoglobin saturation (%SaO2) during sleep as assessed by WatchPAT home sleep study at baseline and week 8.	Baseline, 4 weeks, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of postural therapy as assessed by adherence monitor	Adherence monitor will measure sleep over the set time points and tolerability is defined as a recorded time on the wedge for a minimum of 5 hours.	2, 4, 6 and 8 weeks
Change in average plasma hemoglobin concentration (g/dL)		Baseline, 8 weeks
Change in average Glycated hemoglobin test (HbA1c)	This will measure percentage (%) of HbA1c in the blood.	Baseline, 8 weeks
Change in serum erythropoietin (EPO) concentration	The concentration of EPO in the sample is expressed in International Units per litre (U/L) and is determined by calibration against a reference standard.	Baseline, 8 weeks
Change in soluble Vascular Endothelial Growth Factor (SVEGF-1) concentrations	Plasma levels of SVEGF-1 (pg/mL)	Baseline, 8 weeks
Change in homeostatic model assessment of insulin resistance (HOMA-IR)	Units of measurement is mass units.	Baseline, 8 weeks
Change in total plasma cholesterol level (mg/dL)		Baseline, 8 weeks
Change in plasma low-density lipoprotein (LDL) cholesterol level (mg/dL)		Baseline, 8 weeks
Change in plasma high-density lipoprotein (HDL) cholesterol level (mg/dL)		Baseline, 8 weeks
Change in plasma triglyceride concentration (mg/dL)		Baseline, 8 weeks
Change in Vascular endothelial growth factor receptor 1 (SVEGF-R1) concentration	Units of measurement pg/mL	Baseline, 8 weeks
Change in mean blood pressure (mmHg)		Baseline, 8 weeks
Change in Brachial Artery Reactivity Testing (BART) assessment	Assessed by endothelial function using high-frequency ultrasound visualized brachial artery reactivity testing. Endothelial function is characterized by flow-mediated vasodilation of the brachial artery, which is measured by comparing the brachial artery diameter at rest to the diameter after increased forearm blood flow (reactive hyperemia). Unit of measurement is mass units.	Baseline, 8 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: William Checkley, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 29, 2019
• Primary Completion (ACTUAL): March 15, 2020
• Study Completion (ACTUAL): March 15, 2020

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (ACTUAL): April 25, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes; Respiratory Aspiration; Pulmonary Heart Disease
• Other Study ID Numbers: IRB00170895; R34HL135360 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No