Positive Airway Pressure, Sleep Apnea, and the Placenta (PAP-SAP) (PAP-SAP)

Placental Role in Mediating Adverse Outcomes in Obstructive Sleep Apnea

This study is testing the hypothesis of whether continuous positive airway pressure (CPAP) therapy improves placental histopathology and secretory function. The main aims of the study are to identify shared mechanisms between obstructive sleep apnea and preeclampsia, both common highly morbid conditions.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Sleep; Obstructive Sleep Apnea; Pregnancy; Preeclampsia
• Intervention / Treatment: Device: Positive Airway Pressure; Other: Nasal Dilator Strips

Detailed Description

Patients will be recruited from multiple community and hospital-based practices that care for pregnant women. Subjects will be given a physical exam, have measurements taken, answer questionnaires and then will be screened using a home sleep apnea test (HSAT) Type III device. Those diagnosed with Obstructive Sleep Apnea will then be randomized to one of two groups (below).

Both groups will have:

1. blood testing for placenta-secreted circulating markers
2. placental histopathological and immunohistochemistry examination of placental expression of markers.

Both groups will answer sleep and mood questionnaires, have blood pressure, blood glucose and activity / sleep watch monitoring and will receive an educational session on pregnancy health.

Randomization groups include:

1. Nasal dilator strips: Participants receiving nasal dilator strips will be monitored by need for refill of supplies and periodic phone calls.
2. CPAP + nasal dilator strips: Subjects randomized to positive airway pressure (PAP) therapy will receive auto-titrating PAP. Pressure requirements will be monitored remotely and pressure modified as needed. PAP adherence will be determined subjectively and objectively. This group will also receive nasal dilator strips as described above.

All subjects will receive small gift incentives such as baby-related items. Monetary incentives will also be issued at data collection points.

• Study Type: Interventional
• Enrollment (Estimated): 262
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02904
      • The Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant snorers without obstructive sleep apnea, have a BMI >30 kg/m2 at recruitment
• >18 years of age
• <13 completed weeks of gestation (confirmed by last menstrual period or early pregnancy dating ultrasound during qualification)
• Intention to reside locally and deliver at Women and Infants Hospital of Rhode Island
• Ability to give informed consent.

Exclusion Criteria:

• Unable to meet inclusion criteria, Incompetent cervix / cerclage (likelihood of severe preterm delivery affecting study aims)
• Inability to tolerate PAP therapy
• Serious physical or mental illness or condition that would affect participation
• Drowsy driving
• Severe hypoxemia on sleep study
• Advanced cardiac disease or arrhythmias that may benefit from PAP therapy
• Chronic lung disease and / or respiratory failure.
• Twin pregnancies
• Fetuses with congenital anomalies
• Severe hypertension at enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Positive Airway Pressure; Positive airway pressure and nasal dilator strips during sleep.	Device: Positive Airway Pressure; Auto-titrating PAP + nasal dilator strips during sleep; Other: Nasal Dilator Strips; Nasal dilator strips
Placebo Comparator: Nasal Dilator Strips; Nasal dilator strips during sleep.	Other: Nasal Dilator Strips; Nasal dilator strips

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alterations in circulating placenta-secreted markers.	Placenta secreted markers that have been linked to preeclampsia as well as angiogenic and anti-angiogenic markers will be measured longitudinally during the course of pregnancy.	up to 6 months
Changes in placental histopathology for markers of malperfusion and placental expression of markers	Placental morphology and histopathology will be examined by 3 perinatal pathologists, blinded to each other's reading and to intervention arm. Immunohistochemistry will be used to examine placental expression of certain markers.	Placenta collected at time of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour Ambulatory mean diurnal and nocturnal blood pressure measurements	A 24 blood pressure monitor will be used to measure changes in daytime and nighttime average blood pressure.	Prior to randomization, then at approximately 3 months, and 6 months later
Change in a composite of adverse pregnancy outcomes	Pregnancy outcomes defined as gestational hypertension, gestational diabetes and preterm birth (birth prior to 37 completed weeks of pregnancy will be analyzed as a composite outcome	8 months, delivery and 2 weeks postpartum

Collaborators and Investigators

• Sponsor: The Miriam Hospital
• Collaborators: Brown University; Brigham and Women's Hospital; Rhode Island Hospital; Women and Infants Hospital of Rhode Island
• Investigators: Principal Investigator: Ghada Bourjeily, MD, The Miriam Hospital

Publications and helpful links

General Publications

• Facco F. Sleep Duration, Sleep Timing, and Sleep Disordered Breathing-Associations With Obesity and Gestational Diabetes in Pregnancy. Clin Obstet Gynecol. 2021 Mar 1;64(1):196-203. doi: 10.1097/GRF.0000000000000587.
• Sanapo L, Bublitz MH, Bai A, Mehta N, Messerlian GM, Catalano P, Bourjeily G. Association between sleep disordered breathing in early pregnancy and glucose metabolism. Sleep. 2022 Apr 11;45(4):zsab281. doi: 10.1093/sleep/zsab281.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): August 1, 2020
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: January 21, 2015
• First Submitted That Met QC Criteria: April 8, 2015
• First Posted (Estimated): April 9, 2015

Study Record Updates

• Last Update Posted (Actual): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CPAP; placental morphology; placental secretory function
• Additional Relevant MeSH Terms: Urogenital Diseases; Nervous System Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Hypertension, Pregnancy-Induced; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Pre-Eclampsia; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: 1R01HD078515-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO