Effects of CPAP on Cognitive Function, Neurocognitive Architecture and Function in Patients With OSA: The SMOSAT Trial

Effects of Continuous Positive Airway Pressure on Cognitive Function, Neurocognitive Architecture and Function in Patients With Obstructive Sleep Apnea: The Shanghai Multicenter Obstructive Sleep Apnea Therapy Trial

Multiple clinical studies have indicated that obstructive sleep apnea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicenter trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment, and to explore the role of gut microbiota in improving neurocognitive function during treatment.This study will be a multicenter, randomized, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with severe OSA will be enrolled from five sleep centers, and randomized to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function, and arterial stiffness will be assessed at baseline before randomization and at 3, 6, and 12 months. In addition, the investigators will enroll 74 healthy controls and assess all of the aforementioned variables at baseline.

Study Overview

• Status: Completed
• Conditions: Apnea, Sleep
• Intervention / Treatment: Device: CPAP; Dietary supplement: BSC

Detailed Description

Background Multiple clinical studies have indicated that obstructive sleep apnea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicenter trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment, and to explore the role of gut microbiota in improving neurocognitive function during treatment.

Methods/Design This study will be a multicenter, randomized, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with severe OSA will be enrolled from five sleep centers, and randomized to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function, and arterial stiffness will be assessed at baseline before randomization and at 3, 6, and 12 months. In addition, the investigators will enroll 74 healthy controls and assess all of the aforementioned variables at baseline.

Ethics and Dissemination Ethics approval was given by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The findings from this study will be disseminated in peer-reviewed journals and at conferences.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 2002333
      • Otolaryngological Institute of Shanghai Jiao Tong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent
2. Age 30-65 years
3. Newly diagnosed OSA (full-night in-laboratory polysomnography [PSG] with AHI ≥ 15 events per hour)
4. Adherence to CPAP treatment
5. No participation in any other clinical trial in the past 3 months
6. Able to accomplish relevant tests and follow-up

Exclusion Criteria:

1. Severe systemic diseases (e.g., cardiac, hepatic, and renal failure)
2. Psychiatric conditions (e.g., depression, mania, schizophrenia)
3. Neurological diseases (e.g., head trauma, brain tumor, epilepsy, stroke, transient ischemic attack, coma)
4. Sleep disorders other than OSA (narcolepsy, insomnia, chronic sleep deprivation, rapid eye movement [REM] behavior disorder and restless legs syndrome, central sleep apnea or obesity hypoventilation syndrome)
5. Alcoholism, drug addiction, use of psychotropic drugs, sedatives, or narcotics
6. Prior therapy for OSA (i.e., CPAP, upper airway surgery, oral appliance)
7. Minimum Mental State Examination (MMSE)< 24
8. Left-handed
9. MRI contraindications (e.g., claustrophobic or metal implantation)
10. Gastrointestinal surgery during the last year, except for appendicitis and hernia surgery
11. Pregnancy
12. Use of intestinal flora regulator (e.g., antibiotics or probiotics) in the previous 8 weeks
13. Medical treatment for cholecystitis, gallstones, gastrointestinal ulcers, urinary tract infection, acute pyelonephritis, or cystitis in the past 3 months
14. Infectious diseases, such as tuberculosis, acquired immune deficiency syndrome
15. Commercial drivers or people deemed to be at risk of driving -related accidents
16. Deemed by the researchers to be suitable for this trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP plus BSC; Participants in the CPAP plus BSC group will receive CPAP treatment plus the aforementioned BSC intervention. CPAP treatment (LOTUS AUTO; Curative Medical Technology Inc., Beijing, China) will be initiated using standard clinical practice at each center.	Device: CPAP; CPAP plus BSC group Participants in the CPAP plus BSC group will receive CPAP treatment plus the aforementioned BSC intervention. CPAP treatment (LOTUS AUTO; Curative Medical Technology Inc., Beijing, China) will be initiated using standard clinical practice at each center. Participants in both groups will be asked to continue their usual medical care during the trial.; Dietary supplement: BSC; BSC only group Participants in the BSC only group will receive advice regarding lifestyle modification, sleep hygiene, naps, exercise, caffeine, and diet, and avoiding alcohol consumption, but no specific weight loss program, diet, or salt restriction will be suggested.
Active Comparator: BSC intervention; Participants in the BSC only group will receive advice regarding lifestyle modification, sleep hygiene, naps, exercise, caffeine, and diet, and avoiding alcohol consumption, but no specific weight loss program, diet, or salt restriction will be suggested.	Dietary supplement: BSC; BSC only group Participants in the BSC only group will receive advice regarding lifestyle modification, sleep hygiene, naps, exercise, caffeine, and diet, and avoiding alcohol consumption, but no specific weight loss program, diet, or salt restriction will be suggested.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline neurocognitive function in participants at 3 month,6 month,1 year follow-up as measured by montreal cognitive assessment-score range 0-30	Assessment of neurocognitive function by montreal cognitive assessment-score range 0-30	baseline,month 3, month 6 and year 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline daytime sleepiness and sleep variables in participants at 3 month, 6 month and 1 year follow-up as measured by polysomnography (PSG)	Assessment of daytime sleepiness and sleep variables by PSG	baseline,month 3, month 6 and year 1
Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by central auditory processing testing	Assessment of neurocognitive function by central auditory processing testing	baseline,month 3, month 6 and year 1
Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by 256-channel high-density electroencephalography (EEG) recordings	Assessment of neurocognitive function by 256-channel high-density electroencephalography (EEG) recordings	baseline,month 3, month 6 and year 1
Changes from baseline gut microbiomes in stool specimens in participants at 3 month, 6 month and 1 year follow-up as measured through metagenomic analysis	The bacterial genomic DNA was extracted from tool of participants,V1-V3 hypervariable regions of 16S rRNA were amplified by PCR from DNA using barcoded fusion primers,after the PCR products were extracted and quantified, they were pooled in equimolar concentrations and were sequenced using a 454 Life Sciences Genome Sequencer FLX system	baseline,month 3, month 6 and year 1
Changes from baseline metabolomics profiling in participants at 3 month, 6 month and 1 year follow-up as measured by metabolomics approach	Metabolomics profiling will be detected by a combination of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS)	baseline,month 3, month 6 and year 1
Changes from baseline arterial stiffness (pulse wave velocity, ankle brachial index, toe-brachial) in participants at 3 month, 6 month and 1 year follow-up as measured by echocardiography	Assessment of arterial stiffness	baseline,month 3, month 6 and year 1
Changes from baseline general heart function (left ventricular volume and ejection fraction)in participants at 3 month, 6 month and 1 year follow-up as measured by echocardiography	Assessment of general heart function	baseline,month 3, month 6 and year 1
Changes from baseline body fat distribution in participants at 3 month, 6 month and 1 year follow-up	Assessment of body fat distribution ( abdominal subcutaneous fat,abdominal visceral fat, intrahepatic lipid) by means of magnetic resonance imaging	baseline,month 3, month 6 and year 1
Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by the neuropsychological tests.	The neuropsychological tests includes mental arithmetic,memory scanning, movement perception,switching attention,space location memory span,attention allocation choice reaction time curve fit	baseline,month 3, month 6 and year 1
Changes from baseline Optic nerve fiber layer thickness in participants at 3 month, 6 month and 1 year follow-up as measured by optical coherence tomography	Assessment of Optic nerve fiber layer thickness by optical coherence tomography	baseline,month 3, month 6 and year 1
Changes from baseline neurocognitive function in participants at 3 month,6 month,1 year follow-up as measured by minimum mental state examination-score range 0-30 and functional magnetic resonance imaging	Assessment of neurocognitive function by minimum mental state examination-score range 0-30 and functional magnetic resonance imaging	baseline,month 3, month 6 and year 1

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
• Investigators: Principal Investigator: Shankai Yin, MD, Ph D, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Publications and helpful links

General Publications

• Henderson LA, Fatouleh RH, Lundblad LC, McKenzie DK, Macefield VG. Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea. Front Neurosci. 2016 Mar 10;10:90. doi: 10.3389/fnins.2016.00090. eCollection 2016.
• Dalmases M, Sole-Padulles C, Torres M, Embid C, Nunez MD, Martinez-Garcia MA, Farre R, Bargallo N, Bartres-Faz D, Montserrat JM. Effect of CPAP on Cognition, Brain Function, and Structure Among Elderly Patients With OSA: A Randomized Pilot Study. Chest. 2015 Nov;148(5):1214-1223. doi: 10.1378/chest.15-0171.
• Rosenzweig I, Glasser M, Crum WR, Kempton MJ, Milosevic M, McMillan A, Leschziner GD, Kumari V, Goadsby P, Simonds AK, Williams SC, Morrell MJ. Changes in Neurocognitive Architecture in Patients with Obstructive Sleep Apnea Treated with Continuous Positive Airway Pressure. EBioMedicine. 2016 May;7:221-9. doi: 10.1016/j.ebiom.2016.03.020. Epub 2016 Mar 25.
• Xu H, Wang H, Guan J, Yi H, Qian Y, Zou J, Xia Y, Fu Y, Li X, Jiao X, Huang H, Dong P, Yu Z, Yang J, Xiang M, Li J, Chen Y, Wang P, Sun Y, Li Y, Zheng X, Jia W, Yin S. Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial. BMJ Open. 2017 May 25;7(5):e014932. doi: 10.1136/bmjopen-2016-014932.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2017
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: August 3, 2016
• First Submitted That Met QC Criteria: August 27, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 13, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: OSA; cognitive function; CPAP; gut microbiota; metabolomics
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Apnea Syndromes
• Other Study ID Numbers: 6thShanghaiJiaotongU2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University
• IPD Sharing Time Frame: After 2019
• IPD Sharing Access Criteria: Research institutions
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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