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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Apnea, Sleep

Intervention / Treatment
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* Device: CPAP
* Dietary Supplement: BSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Age 30-65 years Newly diagnosed OSA (full-night in-laboratory polysomnography [PSG] with AHI ≥ 15 events per hour) Adherence to CPAP treatment No participation in any other clinical trial in the past 3 months Able to accomplish relevant tests and follow-up Exclusion Criteria: Severe systemic diseases (e.g., cardiac, hepatic, and renal failure) Psychiatric conditions (e.g., depression, mania, schizophrenia) Neurological diseases (e.g., head trauma, brain tumor, epilepsy, stroke, transient ischemic attack, coma) 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) Alcoholism, drug addiction, use of psychotropic drugs, sedatives, or narcotics Prior therapy for OSA (i.e., CPAP, upper airway surgery, oral appliance) Minimum Mental State Examination (MMSE)< 24 Left-handed MRI contraindications (e.g., claustrophobic or metal implantation) Gastrointestinal surgery during the last year, except for appendicitis and hernia surgery Pregnancy Use of intestinal flora regulator (e.g., antibiotics or probiotics) in the previous 8 weeks Medical treatment for cholecystitis, gallstones, gastrointestinal ulcers, urinary tract infection, acute pyelonephritis, or cystitis in the past 3 months Infectious diseases, such as tuberculosis, acquired immune deficiency syndrome Commercial drivers or people deemed to be at risk of driving -related accidents Deemed by the researchers to be suitable for this trial

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPAP plus BSC<br>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<br>* 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.<br>Dietary Supplement: BSC<br>* 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.<br>|
| Active Comparator: BSC intervention<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OSA, CPAP, cognitive function, gut microbiota, metabolomics