Sleep Disordered Breathing and Cardiopulmonary Disease in Peruvian Highlanders

• ClinicalTrials.gov Identifier: NCT03927547
• Recruitment Status: Completed
• First Posted: April 25, 2019
• Last Update Posted: November 6, 2020
• Sponsor: Johns Hopkins University
• Collaborators: National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Sleep Disordered Breathing; Sleep Apnea	Device: Inclined Sleep	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Subjects will undergo sleep study in subjects' randomized sleep posture. Randomization will be recorded separately from sleep study recordings. These recordings will be reviewed by trained sleep study technicians who will be blinded to randomization. Blood samples will also be assayed for markers of glucose control.
• Primary Purpose: Treatment
• Official Title: Sleep Disordered Breathing and Cardiopulmonary Disease in Peruvian Highlanders
• Actual Study Start Date: September 29, 2019
• Actual Primary Completion Date: March 15, 2020
• Actual Study Completion Date: March 15, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in Respiratory Disturbance Index (RDI) [ Time Frame: Baseline, 4 weeks, 8 weeks ]

   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

2. Change in Mean oxyhemoglobin saturation (percent) during sleep [ Time Frame: Baseline, 4 weeks, 8 weeks ]
   The investigators will measure mean oxyhemoglobin saturation (%SaO2) during sleep as assessed by WatchPAT home sleep study at baseline and week 8.

Secondary Outcome Measures :

1. Tolerability of postural therapy as assessed by adherence monitor [ Time Frame: 2, 4, 6 and 8 weeks ]
   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. Change in average plasma hemoglobin concentration (g/dL) [ Time Frame: Baseline, 8 weeks ]
3. Change in average Glycated hemoglobin test (HbA1c) [ Time Frame: Baseline, 8 weeks ]
   This will measure percentage (%) of HbA1c in the blood.
4. Change in serum erythropoietin (EPO) concentration [ Time Frame: Baseline, 8 weeks ]
   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.
5. Change in soluble Vascular Endothelial Growth Factor (SVEGF-1) concentrations [ Time Frame: Baseline, 8 weeks ]
   Plasma levels of SVEGF-1 (pg/mL)
6. Change in homeostatic model assessment of insulin resistance (HOMA-IR) [ Time Frame: Baseline, 8 weeks ]
   Units of measurement is mass units.
7. Change in total plasma cholesterol level (mg/dL) [ Time Frame: Baseline, 8 weeks ]
8. Change in plasma low-density lipoprotein (LDL) cholesterol level (mg/dL) [ Time Frame: Baseline, 8 weeks ]
9. Change in plasma high-density lipoprotein (HDL) cholesterol level (mg/dL) [ Time Frame: Baseline, 8 weeks ]
10. Change in plasma triglyceride concentration (mg/dL) [ Time Frame: Baseline, 8 weeks ]
11. Change in Vascular endothelial growth factor receptor 1 (SVEGF-R1) concentration [ Time Frame: Baseline, 8 weeks ]
    Units of measurement pg/mL
12. Change in mean blood pressure (mmHg) [ Time Frame: Baseline, 8 weeks ]
13. Change in Brachial Artery Reactivity Testing (BART) assessment [ Time Frame: Baseline, 8 weeks ]

    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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Peru

Prisma Org

Puno, Peru

Sponsors and Collaborators

Johns Hopkins University

National Institutes of Health (NIH)

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: William Checkley; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03927547
• Other Study ID Numbers: IRB00170895; R34HL135360 ( U.S. NIH Grant/Contract )
• First Posted: April 25, 2019
• Last Update Posted: November 6, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Additional relevant MeSH terms:

Sleep Apnea Syndromes; Respiratory Aspiration; Pulmonary Heart Disease; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases