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

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Obese; Pregnancy; Sleep Disordered Breathing
• Interventions: Device: CPAP; Device: sham-CPAP; Other: Sleep hygiene
• Enrollment: 242

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 452 individuals were screened and 355 participants consented for this study . Prior to or during the inital study visit, 113 individuals withdrew or were withdrawn from the study. 242 participants completed visit 1 (14 0/7-20 6/7 weeks gestation, mean gestational age 18.1 ± 2.0 weeks), of whom 89 (37%) had an AHI between 5 and 50 and therefore were eligible for randomization.

Arm/Group Title	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, Sleep Hygiene	Obese SDB CPAP Phase 2
Arm/Group Description	Therapeutic CPAP 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).	Sham (non-therapeutic) CPAP sham-CPAP	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Period Title: Overall Study
Started	25	26	20	18
Completed	24	26	20	16
Not Completed	1	0	0	2
Reason Not Completed
Withdrawal by Subject	1	0	0	2

Baseline Characteristics

Arm/Group Title		Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SDB Positive, CPAP Phase 2	Total
Arm/Group Description		Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP	Total of all reporting groups
Overall Number of Baseline Participants		26	25	20	18	89
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants	25 participants	20 participants	18 participants	89 participants
		26.4 (3.9)	28.4 (6.5)	32.0 (4.5)	32.6 (4.5)	29.6 (5.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	25 participants	20 participants	18 participants	89 participants
	Female	26 100.0%	25 100.0%	20 100.0%	18 100.0%	89 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	25 participants	20 participants	18 participants	89 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	1 5.0%	0 0.0%	1 1.1%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	19 73.1%	16 64.0%	13 65.0%	9 50.0%	57 64.0%
	White	5 19.2%	9 36.0%	6 30.0%	9 50.0%	29 32.6%
	More than one race	2 7.7%	0 0.0%	0 0.0%	0 0.0%	2 2.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound
Description	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.
Time Frame	early pregnancy (14-16 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	25	20	18
Mean (Standard Deviation); Unit of Measure: Mean PI
	1.0 (0.3)	1.0 (0.3)	1.0 (0.3)	1.0 (0.3)

2. Primary Outcome

Title	Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement
Description	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.
Time Frame	early pregnancy (14-16 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	25	20	18
Mean (Standard Deviation); Unit of Measure: Ratio
	53.8 (29.1)	65.1 (45.8)	87.0 (69.1)	88.3 (45.0)

3. Primary Outcome

Title	Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin
Description	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)
Time Frame	early pregnancy (14-16 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	25	20	18
Mean (Standard Deviation); Unit of Measure: HOMA-IR score
	4.5 (3.5)	4.6 (6.4)	3.9 (2.2)	4.2 (3.0)

4. Primary Outcome

Title	Uterine Artery Doppler Mean Pulsatility Index -by Ultrasound
Description	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.
Time Frame	late pregnancy (28-32 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	24	20	16
Mean (Standard Deviation); Unit of Measure: Mean PI
	0.9 (0.2)	0.8 (0.3)	0.8 (0.2)	0.7 (0.1)

5. Primary Outcome

Title	Soluble FMS-like Tyrosine Kinase 1 (sFlt-1)/ Placental Growth Factor (PlGF) Ratio-blood Measurement
Description	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.
Time Frame	late pregnancy (28-32 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	25	20	18
Mean (Standard Deviation); Unit of Measure: Ratio
	30.5 (28.9)	26.0 (18.3)	38.3 (34.7)	45.9 (57.3)

6. Primary Outcome

Title	Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)-Blood Measurement of Glucose and Insulin
Description	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)
Time Frame	late pregnancy (28-32 weeks gestation)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	26	25	20	18
Mean (Standard Deviation); Unit of Measure: HOMA-IR score
	6.3 (10.7)	3.7 (3.6)	3.6 (1.8)	4.6 (6.3)

7. Secondary Outcome

Title	Placental Histology and Immunohistochemistry
Description	placental histology and immunohistochemistry
Time Frame	After delivery (expected 37-40 weeks gestation)

Outcome Measure Data

Analysis Population Description

Placental collection and analysis was not performed due to inadequate staffing and personnel issues

Arm/Group Title	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description:	Sham (non-therapeutic) CPAP sham-CPAP	Therapeutic CPAP 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).	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
Overall Number of Participants Analyzed	0	0	0	0

No data displayed because Outcome Measure has zero total analyzed.

8. Other Pre-specified Outcome

Title	Mean Arterial Blood Pressure (mmHg) Angiogenic Domain
Description	[Not Specified]
Time Frame	early pregnancy (14-16 weeks gestation)

Outcome Measure Data Not Reported

9. Other Pre-specified Outcome

Title	Pregnancy Outcome Data
Description	Preeclampsia, Gestational diabetes, Gestational age at delivery, Indication for delivery, Birthweight, Cord gases
Time Frame	At time of delivery (expected 37-40 weeks gestation)

Outcome Measure Data Not Reported

10. Other Pre-specified Outcome

Title	Mean Arterial Blood Pressure (mmHg) Angiogenic Domain
Description	[Not Specified]
Time Frame	late pregnancy (28-32 weeks gestation)

Outcome Measure Data Not Reported

11. Other Pre-specified Outcome

Title	Soluble Endoglin (sEng ,pg/mL)-Blood Measurement
Description	Endoglin is a coreceptor for transforming growth factor beta-1 and beta-3 expressed on syncytiotrophoblasts
Time Frame	early pregnancy (14-16 weeks gestation)

Outcome Measure Data Not Reported

12. Other Pre-specified Outcome

Title	Soluble Endoglin (sEng , pg/mL)-Blood Measurement
Description	Endoglin is a coreceptor for transforming growth factor beta-1 and beta-3 expressed on syncytiotrophoblasts
Time Frame	late pregnancy (28-32 weeks gestation)

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From enrollment to 6 weeks post partum, an average of 1 year
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
Arm/Group Description	Therapeutic CPAP 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).	Sham (non-therapeutic) CPAP sham-CPAP	Sleep hygiene information and local sleep resources Sleep hygiene: Information about sleep apnea and healthy sleep. Information about local sleep resources	Therapeutic CPAP
All-Cause Mortality
	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/25 (0.00%)	0/26 (0.00%)	0/20 (0.00%)	0/18 (0.00%)
Serious Adverse Events
	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/25 (4.00%)	0/26 (0.00%)	0/20 (0.00%)	1/18 (5.56%)
Pregnancy, puerperium and perinatal conditions
Maternal ICU admission †	0/25 (0.00%)	0/26 (0.00%)	0/20 (0.00%)	1/18 (5.56%)
Fetal Demise †	1/25 (4.00%)	0/26 (0.00%)	0/20 (0.00%)	0/18 (0.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Obese, SDB Postive, CPAP, Phase 1	Obese, SDB Postive, Sham-CPAP	Obese, SDB Postive, Sleep Hygiene	Obese, SBD Positive, CPAP, Phase 2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/25 (0.00%)	3/26 (11.54%)	0/20 (0.00%)	1/18 (5.56%)
Cardiac disorders
EKG abnormality †	0/25 (0.00%)	1/26 (3.85%)	0/20 (0.00%)	0/18 (0.00%)
Respiratory, thoracic and mediastinal disorders
CPAP complication † [1]	0/25 (0.00%)	1/26 (3.85%)	0/20 (0.00%)	1/18 (5.56%)
Skin and subcutaneous tissue disorders
Rash †	0/25 (0.00%)	1/26 (3.85%)	0/20 (0.00%)	0/18 (0.00%)
† Indicates events were collected by systematic assessment; [1] When attempting to use the CPAP machine she is waking up in the middle of the night coughing and needing to catch her breath.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Francesca Facco
• Organization: University of Pittsburgh
• Phone: 412-641-1220
• EMail: Faccof@upmc.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Francesca Facco, MD, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02086448
• Other Study ID Numbers: PRO13080159; R01HL120354 ( U.S. NIH Grant/Contract ); K12HD043441 ( U.S. NIH Grant/Contract )
• First Submitted: February 18, 2014
• First Posted: March 13, 2014
• Results First Submitted: November 2, 2021
• Results First Posted: March 8, 2022
• Last Update Posted: March 22, 2023