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

Primary Purpose

Apnea, Sleep

Status

Completed

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

CPAP

BSC

About this trial

This is an interventional treatment trial for Apnea, Sleep focused on measuring OSA, CPAP, cognitive function, gut microbiota, metabolomics

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Otolaryngological Institute of Shanghai Jiao Tong University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

CPAP plus BSC

BSC intervention

Arm Description

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 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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

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)

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

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

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

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

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

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

Full Information

NCT ID

NCT02886156

First Posted

August 3, 2016

Last Updated

February 13, 2022

Sponsor

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02886156

Brief Title

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

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

April 4, 2017 (Actual)

Primary Completion Date

December 30, 2021 (Actual)

Study Completion Date

December 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Apnea, Sleep

Keywords

OSA, CPAP, cognitive function, gut microbiota, metabolomics

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

148 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CPAP plus BSC

Arm Type

Experimental

Arm Description

Arm Title

BSC intervention

Arm Type

Active Comparator

Arm Description

Intervention Type

Device

Intervention Name(s)

CPAP

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

BSC

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Assessment of neurocognitive function by montreal cognitive assessment-score range 0-30

Time Frame

baseline,month 3, month 6 and year 1

Secondary Outcome Measure Information:

Title

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)

Description

Assessment of daytime sleepiness and sleep variables by PSG

Time Frame

baseline,month 3, month 6 and year 1

Title

Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by central auditory processing testing

Description

Assessment of neurocognitive function by central auditory processing testing

Time Frame

baseline,month 3, month 6 and year 1

Title

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

Description

Assessment of neurocognitive function by 256-channel high-density electroencephalography (EEG) recordings

Time Frame

baseline,month 3, month 6 and year 1

Title

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

Description

Time Frame

baseline,month 3, month 6 and year 1

Title

Changes from baseline metabolomics profiling in participants at 3 month, 6 month and 1 year follow-up as measured by metabolomics approach

Description

Time Frame

baseline,month 3, month 6 and year 1

Title

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

Description

Assessment of arterial stiffness

Time Frame

baseline,month 3, month 6 and year 1

Title

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

Description

Assessment of general heart function

Time Frame

baseline,month 3, month 6 and year 1

Title

Changes from baseline body fat distribution in participants at 3 month, 6 month and 1 year follow-up

Description

Assessment of body fat distribution ( abdominal subcutaneous fat,abdominal visceral fat, intrahepatic lipid) by means of magnetic resonance imaging

Time Frame

baseline,month 3, month 6 and year 1

Title

Changes from baseline neurocognitive function in participants at 3 month, 6 month and 1 year follow-up as measured by the neuropsychological tests.

Description

The neuropsychological tests includes mental arithmetic,memory scanning, movement perception,switching attention,space location memory span,attention allocation choice reaction time curve fit

Time Frame

baseline,month 3, month 6 and year 1

Title

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

Description

Assessment of Optic nerve fiber layer thickness by optical coherence tomography

Time Frame

baseline,month 3, month 6 and year 1

Title

Description

Assessment of neurocognitive function by minimum mental state examination-score range 0-30 and functional magnetic resonance imaging

Time Frame

baseline,month 3, month 6 and year 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shankai Yin, MD, Ph D

Organizational Affiliation

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Otolaryngological Institute of Shanghai Jiao Tong University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

2002333

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University

IPD Sharing Time Frame

After 2019

IPD Sharing Access Criteria

Research institutions

Citations:

PubMed Identifier

27013952

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.

Results Reference

background

PubMed Identifier

26065720

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.

Results Reference

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PubMed Identifier

27322475

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.

Results Reference

background

PubMed Identifier

28550021

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.

Results Reference

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

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