Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP) (SOAP)

• ClinicalTrials.gov Identifier: NCT02086448
• Recruitment Status: Completed
• First Posted: March 13, 2014
• Results First Posted: March 8, 2022
• Last Update Posted: March 22, 2023
• Sponsor: Francesca Facco, MD
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Francesca Facco, MD, University of Pittsburgh

Tracking Information

• First Submitted Date: February 18, 2014
• First Posted Date: March 13, 2014
• Results First Submitted Date: November 2, 2021
• Results First Posted Date: March 8, 2022
• Last Update Posted Date: March 22, 2023
• Study Start Date: September 2014
• Actual Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 10, 2022)

• Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound [ Time Frame: early pregnancy (14-16 weeks gestation) ]
  The uterine artery was located using color doppler imaging by placing the ultrasound probe in the right or left iliac fossa in the sagittal plane. The uterine artery was then identified where it crosses the external iliac artery. Doppler waveform was obtained using a sampling gate encompassing the width of the main uterine artery at an angle of insonation of <30 degrees if possible. The PI was calculated using the formula: maximum-minimum velocity/mean velocity.
• Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement [ Time Frame: early pregnancy (14-16 weeks gestation) ]
  sFlt-1 is a splice variant of vascular endothelial growth receptor (VEGF) with antiangiogenic properties that is upregulated in preeclampsia. PlGF is an angiogenic cytokine that is highly expressed in the placenta. Low levels have been associated with preeclampsia.
• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin [ Time Frame: early pregnancy (14-16 weeks gestation) ]
  Insulin resistance was calculated using the homeostatic model assessment for insulin resistance (HOMA-IR, fasting insulin (µU/mL) x fasting glucose (mmol/L) /22.5)
• Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound [ Time Frame: late pregnancy (28-32 weeks gestation) ]
  The uterine artery was located using color doppler imaging by placing the ultrasound probe in the right or left iliac fossa in the sagittal plane. The uterine artery was then identified where it crosses the external iliac artery. Doppler waveform was obtained using a sampling gate encompassing the width of the main uterine artery at an angle of insonation of <30 degrees if possible. The PI was calculated using the formula: maximum-minimum velocity/mean velocity.
• Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement [ Time Frame: late pregnancy (28-32 weeks gestation) ]
  sFlt-1 is a splice variant of vascular endothelial growth receptor (VEGF) with antiangiogenic properties that is upregulated in preeclampsia. PlGF is an angiogenic cytokine that is highly expressed in the placenta. Low levels have been associated with preeclampsia.
• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin [ Time Frame: late pregnancy (28-32 weeks gestation) ]
  Insulin resistance was calculated using the homeostatic model assessment for insulin resistance (HOMA-IR, fasting insulin (µU/mL) x fasting glucose (mmol/L) /22.5)

Original Primary Outcome Measures (submitted: March 11, 2014)

• Uterine artery Doppler mean pulsatility index -by ultrasound [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• sFLT/PIGF ratio-blood measurement [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• Homeostasis model assessment of insulin resistance (HOMA-IR)-blood measurement of glucose and insulin [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• Uterine artery Doppler mean pulsatility index -by ultrasound [ Time Frame: late pregnancy (28-32 weeks gestation) ]
• sFLT/PIGF ratio-blood measurement [ Time Frame: late pregnancy (28-32 weeks gestation) ]
• Homeostasis model assessment of insulin resistance (HOMA-IR)-blood measurement of glucose and insulin [ Time Frame: late pregnancy (28-32 weeks gestation) ]

Current Secondary Outcome Measures (submitted: February 27, 2023)

Placental Histology and Immunohistochemistry [ Time Frame: After delivery (expected 37-40 weeks gestation) ]

placental histology and immunohistochemistry

• Original Secondary Outcome Measures (submitted: March 11, 2014): placental histology and immunohistochemistry [ Time Frame: After delivery (expected 37-40 weeks gestation) ]

Current Other Pre-specified Outcome Measures (submitted: February 10, 2022)

• Mean Arterial Blood Pressure (mmHg) Angiogenic Domain [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• Pregnancy Outcome Data [ Time Frame: At time of delivery (expected 37-40 weeks gestation) ]
  Preeclampsia, Gestational diabetes, Gestational age at delivery, Indication for delivery, Birthweight, Cord gases
• Mean Arterial Blood Pressure (mmHg) Angiogenic Domain [ Time Frame: late pregnancy (28-32 weeks gestation) ]
• Soluble Endoglin (sEng ,pg/mL)-Blood Measurement [ Time Frame: early pregnancy (14-16 weeks gestation) ]
  Endoglin is a coreceptor for transforming growth factor beta-1 and beta-3 expressed on syncytiotrophoblasts
• Soluble Endoglin (sEng , pg/mL)-Blood Measurement [ Time Frame: late pregnancy (28-32 weeks gestation) ]
  Endoglin is a coreceptor for transforming growth factor beta-1 and beta-3 expressed on syncytiotrophoblasts

Original Other Pre-specified Outcome Measures (submitted: March 11, 2014)

• Mean arterial blood pressure (mmHg) Angiogenic Domain [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• Pregnancy outcome data [ Time Frame: At time of delivery (expected 37-40 weeks gestation) ]
  Preeclampsia, Gestational diabetes, Gestational age at delivery, Indication for delivery, Birthweight, Cord gases
• Mean arterial blood pressure (mmHg) Angiogenic Domain [ Time Frame: late pregnancy (28-32 weeks gestation) ]
• sEng (pg/mL)-blood measurement [ Time Frame: early pregnancy (14-16 weeks gestation) ]
• sEng (pg/mL)-blood measurement [ Time Frame: late pregnancy (28-32 weeks gestation) ]

Descriptive Information

• Brief Title: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP)
• Official Title: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP)
• Brief Summary: The purpose of this study is to better understand how sleep apnea, a common sleep disorder in which a person has one or more pauses in breathing or shallow breaths while sleeping, may affect pregnancy and to determine the effect of Continuous Positive Airway Pressure (CPAP), a treatment that uses mild air pressure to keep the airways open during sleep, for pregnant women with sleep apnea.

Detailed Description

Emerging data support a link between sleep disordered breathing (SDB) and adverse pregnancy outcomes, particularly preeclampsia. Furthermore, SDB, which is characterized by intermittent nocturnal hypoxia-reoxygenation as well as sleep disruption, results in endothelial dysfunction and metabolic dysregulation, the same biological pathways that have been associated with adverse pregnancy outcomes. Obesity is a well-known risk factor for both adverse pregnancy outcomes and SDB, and has been associated with the same aforementioned biological aberrations. Therefore, obesity complicates the definition of a causal relationship between SDB and pregnancy outcomes. While some classic cardiovascular risk factors (prehypertension) are certainly relevant in pregnancy, there are also well-established risk factors that are unique to pregnancy (uterine vascular stiffness, placental angiogenic factors). The interplay between SDB, obesity and these unique cardiovascular risk factors remains undefined, and this proposal aims to address this knowledge gap. Without this data, our ability to understand how we can mitigate these risks through the use of therapeutic interventions for SDB, such as CPAP (continuous positive airway pressure), is compromised. To further address this knowledge gap, we will make use of the placenta's ability to accumulate evidence of damage over time and provide a record of maternal vascular health throughout gestation. Numerous placental lesions deriving from maternal vascular disease have been identified and can be readily detected on placental pathology. These lesions can provide a measure of the severity of hypoxic stress experienced by the fetus during gestation.

The investigators' central hypothesis is that SDB is an effect modifier that increases maternal cardiovascular risk and placental hypoxic injury in obese pregnant women, and that CPAP treatment during pregnancy will result in an improved cardiovascular risk and placental profile. To test this hypothesis the investigaotrs will identify a cohort of obese women both with and without SDB. The investigators will examine SDB's impact on maternal vascular stiffness (uterine artery Doppler), angiogenesis (pregnancy specific angiogenic factors e.g., sFLT-1) and metabolism (insulin resistance) across pregnancy (Aim 1). The investigators will perform a randomized controlled trial of autotitrating- CPAP verses sham-CPAP in pregnancy to examine the impact of CPAP treatment during pregnancy on cardiovascular risk (Aim 2) and will explore the interplay between SDB, CPAP and evidence of maternal vascular disease and chronic fetal hypoxia by evaluating the placental profile of obese women with and without SDB (Aim 3).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Obese
• Pregnancy
• Sleep Disordered Breathing

Intervention

• Device: CPAP
  CPAP is a device that has a mask worn over the nose that is attached to a device that provides positive airway pressure. CPAP is worn while sleeping, it splints open the airway and prevents apneas (cessation of breathing) and hypopneas (reduced airflow while breathing).
  Other Name: Continuous Positive Airway Pressure
• Device: sham-CPAP
• Other: Sleep hygiene
  Information about sleep apnea and healthy sleep. Information about local sleep resources

Study Arms

• No Intervention: Obese, SDB negative
  No intervention, observational comparison group
• Active Comparator: Obese, SDB postive, CPAP
  Therapeutic CPAP
  Intervention: Device: CPAP
• Sham Comparator: Obese, SDB postive, sham-CPAP
  Sham (non-therapeutic) CPAP
  Intervention: Device: sham-CPAP
• Obese, SDB postive, sleep hygiene
  Sleep hygiene information and local sleep resources
  Intervention: Other: Sleep hygiene

• Publications *: Onslow ML, Wolsk J, Wisniewski S, Patel S, Gallaher M, Hubel C, Cashmere DJ, Facco FL. The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity. J Clin Sleep Med. 2023 Jan 1;19(1):97-109. doi: 10.5664/jcsm.10254.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 10, 2022): 242
• Original Estimated Enrollment (submitted: March 11, 2014): 16
• Actual Study Completion Date: February 2022
• Actual Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• women between 14 0/7 and 20 6/7 weeks gestation at the time of their initial PSG assessment.
• Pregnancy and current BMI >=30
• Self-reported frequent snoring (>=3x/week over past month) or self-reported non-snorer.

Exclusion Criteria:

• diagnosis of pregestational diabetes.
• self-report a history of sleep apena and who are using or were receommended by a physican to use a PAP device already
• twins

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02086448
• Other Study ID Numbers: PRO13080159; R01HL120354 ( U.S. NIH Grant/Contract ); K12HD043441 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Francesca Facco, MD, University of Pittsburgh
• Original Responsible Party: Francesca Facco, MD, University of Pittsburgh, Principal Investigator
• Current Study Sponsor: Francesca Facco, MD
• Original Study Sponsor: University of Pittsburgh

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Francesca Facco, MD; University of Pittsburgh

• PRS Account: University of Pittsburgh
• Verification Date: February 2023