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

Shanghai Jiao Tong University Affiliated Sixth People's Hospital148 enrolled

Overview

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.

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.

Interventions

CPAPDEVICE

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.

BSCDIETARY_SUPPLEMENT

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.

Eligibility

Sex: ALLMin age: 30 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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