Effects of CPAP on Cognitive Function, Neurocognitive Architecture and Function in Patients With OSA: The SMOSAT Trial
- Conditions
- Apnea, Sleep
- Interventions
- Device: CPAPDietary Supplement: BSC
- Registration Number
- NCT02886156
- Lead Sponsor
- Shanghai Jiao Tong University Affiliated Sixth People's Hospital
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 148
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPAP plus BSC CPAP 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. CPAP plus BSC 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. BSC intervention BSC 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.
- Primary Outcome Measures
Name Time Method 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 baseline,month 3, month 6 and year 1 Assessment of neurocognitive function by montreal cognitive assessment-score range 0-30
- Secondary Outcome Measures
Name Time Method 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 baseline,month 3, month 6 and year 1 Assessment of Optic nerve fiber layer thickness by optical coherence tomography
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) baseline,month 3, month 6 and year 1 Assessment of daytime sleepiness and sleep variables by PSG
Changes from baseline metabolomics profiling in participants at 3 month, 6 month and 1 year follow-up as measured by metabolomics approach baseline,month 3, month 6 and year 1 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)
Changes from baseline body fat distribution in participants at 3 month, 6 month and 1 year follow-up baseline,month 3, month 6 and year 1 Assessment of body fat distribution ( abdominal subcutaneous fat,abdominal visceral fat, intrahepatic lipid) by means of magnetic resonance imaging
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 baseline,month 3, month 6 and year 1 Assessment of neurocognitive function by minimum mental state examination-score range 0-30 and functional magnetic resonance imaging
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 baseline,month 3, month 6 and year 1 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
Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by central auditory processing testing baseline,month 3, month 6 and year 1 Assessment of neurocognitive function by central auditory processing testing
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 baseline,month 3, month 6 and year 1 Assessment of general heart function
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 baseline,month 3, month 6 and year 1 Assessment of neurocognitive function by 256-channel high-density electroencephalography (EEG) recordings
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 baseline,month 3, month 6 and year 1 Assessment of arterial stiffness
Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by the neuropsychological tests. baseline,month 3, month 6 and year 1 The neuropsychological tests includes mental arithmetic,memory scanning, movement perception,switching attention,space location memory span,attention allocation choice reaction time curve fit
Trial Locations
- Locations (1)
Otolaryngological Institute of Shanghai Jiao Tong University
🇨🇳Shanghai, Shanghai, China