Clinical trial NCT02886156: Effects of CPAP on Cognitive Function, Neurocognitive Architecture and Function in Patients With OSA: The SMOSAT Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Apnea, Sleep
Keywords: OSA
CPAP
cognitive function
gut microbiota
metabolomics
Lead sponsor: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Sponsor class: OTHER
First posted: 2016-09-01
Enrollment: 148
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
Secondary outcomes:
measure: 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)
timeFrame: baseline,month 3, month 6 and year 1
measure: Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by central auditory processing testing
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
measure: Changes from baseline metabolomics profiling in participants at 3 month, 6 month and 1 year follow-up as measured by metabolomics approach
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
measure: Changes from baseline body fat distribution in participants at 3 month, 6 month and 1 year follow-up
timeFrame: baseline,month 3, month 6 and year 1
measure: Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by the neuropsychological tests.
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
measure: 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
timeFrame: baseline,month 3, month 6 and year 1
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Otolaryngological Institute of Shanghai Jiao Tong University
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University Affiliated Sixth People's Hospital
name: Shankai Yin, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.