Apnea, Sleep
Conditions
Keywords
OSA, CPAP, cognitive function, gut microbiota, metabolomics
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.
Interventions
DEVICECPAP
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_SUPPLEMENTBSC
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.
Sponsors
Shanghai Jiao Tong University Affiliated Sixth People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 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 |
| 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 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 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 |
Countries
China
Outcome results
None listed