Obstructive Sleep ApneaNCT06608888
Unveiling the Neural Mechanisms of 5-HT7 in Sleep Apnea Induced by Arousal Dysregulation
An observational study of Obstructive Sleep Apnea, run by Beijing Tsinghua Chang Gung Hospital at 1 site in China.
Trial summary
Obstructive sleep apnea (OSA), recognized as a highly prevalent sleep breathing disorder with severe complications, features a complex etiology. Poor understanding of disease pathogenesis limits the overall efficacy of interventions. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- MRI
- How many people
- 140 participants
- Where
- 1 siteChina
- Study dates
- 30 Aug 2024to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Snoring Population: Individuals who regularly experience snoring during sleep, often resulting in loud and disruptive noises. Healthy Volunteer Population: Individuals characterized by the absence of sleep disorders or other health conditions that could affect sleep quality. These volunteers typically exhibit regular sleep patterns without snoring or sleep-disordered breathing and meet specific age and health criteria to ensure they represent a healthy comparison group. OSA (Obstructive Sleep Apnea) Patient Population: Patients diagnosed with OSA, a sleep disorder where the airway collapses or becomes blocked repeatedly during sleep.OSA is typically confirmed through an overnight sleep study that measures breathing interruptions and oxygen desaturation events.
Who may be able to join
- OSA Patients:
- Age between 20 and 60 years.
- Symptoms of sleep snoring and daytime sleepiness.
- Confirmed diagnosis of OSA following overnight sleep monitoring.
- Simple Snorers:
- Age between 20 and 60 years.
Show all 12Show fewer
- Symptoms of sleep snoring.
- Overnight sleep monitoring indicates not meeting the OSA diagnosis.
- Healthy Controls:
- Age between 20 and 60 years.
- No symptoms of sleep snoring.
- Overnight sleep monitoring rules out the diagnosis of OSA.
Who cannot join
- Presence of severe pulmonary, neurological, or cardiovascular complications.
- History of long-term non-invasive positive pressure ventilation treatment (more than 3 months) or upper airway surgery.
- Sleep-disordered breathing due to special etiologies such as hypothyroidism, acromegaly, vocal cord paralysis, etc.
- Presence of severe mental illness, long-term alcohol abuse, or a history of prolonged use of sedative-hypnotic drugs.
- Central sleep apnea predominant sleep disorders due to various causes.
- Severe craniofacial deformities, myasthenia gravis, or other known myopathic histories.
- Patients with peripheral neuropathy caused by diabetes, autoimmune diseases, etc.
- Patients with comorbid insomnia, anxiety, depression, or other types of sleep disorders.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
No. 168 Litang Road, Changping District
Beijing, Beijing Municipality, 100028
Yingqian Zhou, 010-56119472, yingqianzhou9112@126.com
Yue Yin, 86-17600807298, yinyue1217@126.com
About this study
Obstructive sleep apnea (OSA), recognized as a highly prevalent sleep breathing disorder with severe complications, features a complex etiology. Poor understanding of disease pathogenesis limits the overall efficacy of interventions. Studies have found that upregulation of 5-HT7 expression in the lateral hypothalamus (LH) could reduce arousal threshold (ArTH) and induce an inhibitory effect to the respiratory central, which was associated with hypoxic stimulation. Therefore, the investigators speculate that the structural/functional abnormalities of the arousal-respiratory neural circuit, mediated by LH5-HT7, may play an important role in the pathogenesis of OSA. To verify the hypothesis, the investigators will compare the ArTH and the brain network presenting by multimodal MRI in normal individuals, snoring individuals, and OSA patients, to reveal the correlation between arousal dysregulation and the structure/function of LH regions; compare the changes of ArTH and brain network in OSA patients with low ArTH before and after CPAP treatment, to verify the interaction between hypoxia and arousal dysregulation, as well as whether the damaging performance of the arousal-respiratory brain regulation area in OSA patients can be partially reversed by relieving hypoxia. Above all, the joint application B team will further analyze the LH5-HT7 neural mechanism in the pathogenesis of OSA.
Read the detailed description
The study consists of two parts: The first part is a cross-sectional study comparing the differences in arousal threshold, loop gain, and the brain network structure and functional connectivity of the brain areas involved in micro-arousal-respiratory center regulation between the non-OSA group (including healthy individuals and those with simple snoring) and the OSA group; The second part is a cohort study, which conducts a three-month longitudinal follow-up of the OSA group to observe the changes in the indicators of the structure and function of the core brain areas related to ArTH and micro-arousal-respiratory center regulation after the correction of intermittent hypoxia through CPAP treatment.The specific research content is as follows:
- ArTH Comparative Analysis Based on Multimodal Assessment of OSA Etiology Select untreated OSA patients, simple snorers (with snoring symptoms, AHI < 5 events/h), and healthy individuals (without snoring symptoms, AHI < 5 events/h), matched for age and gender, and divide them into two groups.Non-OSA group (including healthy individuals and those with simple snoring) and OSA group . After all study participants have undergone upper airway CT, they are all subjected to overnight PSG with synchronous esophageal pressure monitoring, end-tidal carbon dioxide monitoring, and genioglossus electromyography (GGEMG) monitoring. A pharyngeal pressure regulation device is used to induce respiratory events with micro-arousals in the study participants under resistive ventilation, and the trends of ArTH, GGEMG, and respiratory drive (loop gain, LG) are analyzed among different sleep stages. Then, by integrating the above multimodal etiological parameters, the differences in micro-arousal regulation between OSA patients (high airway resistance and hypoxia group), simple snorers (high airway resistance without hypoxia group), and healthy individuals (low airway resistance without hypoxia group) are clarified. Furthermore, the weight of ArTH in the etiology of OSA is calculated, and the individual differences in ArTH among OSA patients and its correlation with the severity of the disease are analyzed.
- Feature Analysis of OSA Micro-arousal-Respiratory Central Regulation Network Based on Multimodal MRI By integrating multimodal MRI imaging data, including structural T1, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), the differences in brain network structure and functional connectivity of brain regions involved in micro-arousal-respiratory central regulation between OSA patients, simple snorers, and healthy individuals with different ArTH levels are compared. This reveals the patterns of functional connectivity changes and structural basis related to micro-arousal abnormal regulation in OSA patients, and clarifies the correlation with the lateral hypothalamus (LH) brain region.
- Comparative Analysis of LH-Related Brain Region Structure and ArTH in OSA Patients with Low ArTH Before and After CPAP Treatment After OSA patients with different ArTH levels have undergone more than 6 months of CPAP treatment, ArTH and multimodal MRI imaging data (T1, DTI, rs-fMRI) are re-measured to observe the changes in ArTH and the structure/function of the core brain regions regulating micro-arousal-respiratory central in OSA patients after correcting intermittent hypoxia with CPAP treatment. These changes are compared with the ArTH and brain network structure of healthy controls to verify the damaging effects of hypoxia on brain networks and to clarify whether the damaging manifestations of the micro-arousal-respiratory central regulation regions in OSA patients can be partially reversed with treatment.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- MRI
- Keywords
- Obstructive Sleep Apnea, Arousal Dysregulation, Arousal Threshold, Lateral Hypothalamus, 5-HT7 Receptor
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
Also called PSG, Genioglossus Electromyography
Multimodal MRI technology is a method that combines various magnetic resonance imaging techniques, providing more comprehensive images and information about human tissues and organs. These different imaging techniques include, but are not limited to:
Structural MRI (sMRI): Provides information about the types of brain tissues, such as gray matter, white matter, and cerebrospinal fluid.
Functional MRI (fMRI): Dynamically measures the hemodynamic response related to brain neural activity, commonly used to study brain functional activities.
Diffusion Tensor Imaging (DTI): Offers information on the structural connections between brain regions, which can be used to study the neural fiber pathways of the brain
| Study group | Role | What they receive |
|---|---|---|
| Non-OSA patients group | Healthy individuals (without snoring symptoms, AHI < 5 events/h)；Simple snorers (with snoring symptoms, AHI < 5 events/h) Receives: Diagnostic Test: MRI | |
| OSA patients | Patients diagnosed with OSA Receives: Diagnostic Test: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arousal threshold
Calculate the patient's arousal threshold based on PSG results.
Measured: Three-month follow-up
Fractional anisotropy
The fractional anisotropy (FA) value, obtained through diffusion tensor imaging (DTI) measurements, was used to compare the brain functions between patients with obstructive sleep apnea (OSA) and those without. Additionally, a follow-up was conducted after three months of continuous positive airway pressure (CPAP) treatment for OSA patients to compare the FA values before and after treatment, thereby clarifying the changes in patients' brain functions.
Measured: After three months of CPAP treatment, DTI were taken again on OSA patients to calculate the FA values.
Connectivity strength
The investigators conducted functional MRI measurements on patients with obstructive sleep apnea (OSA) and non-OSA volunteers, calculated functional connectivity, and compared the differences in their results. Subsequently, the investigators followed up with the OSA patients who underwent three months of CPAP therapy and compared the functional connectivity of brain regions before and after treatment to clarify changes in patients' brain functions.
Measured: After three months of CPAP treatment, fMRI were taken again on OSA patients to calculate connectivity strength.
Secondary outcomes (3)
Sleep Stage Distribution
One of the indicators in PSG results.
Measured: Three-month follow-up
Apnea-Hypopnea Index
One of the indicators in PSG results.
Measured: Three-month follow-up
Oxygen Saturation
One of the indicators in PSG results.
Measured: Three-month follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2024
- Study start30 Aug 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies of the same condition, open and under way.
- More trials run by Beijing Tsinghua Chang Gung HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tsinghua Chang Gung Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jingying Ye, Beijing Tsinghua Chang Gung Hospital
- Investigators
- Jingying Ye, Principal investigator, BeijingTsinghua Changgung Hospital，Tsinghua University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06608888
- Sponsor's protocol ID
- 23657-0-01
- Other IDs
- 82341247
- Status last verified
- Sep 2024
- First submitted
- 16 Sep 2024
- Last updated
- 26 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: all IPD that underlie results in a publication
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unveiling the Neural Mechanisms of 5-HT7 in Sleep Apnea Induced by Arousal Dysregulation
- ClinicalTrials.gov ID
- NCT06608888
- Acronym / sponsor ID
- 23657-0-01
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Obstructive Sleep Apnea, Arousal Dysregulation, Arousal Threshold, Lateral Hypothalamus, 5-HT7 Receptor
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Beijing Tsinghua Chang Gung HospitalUniversity, hospital or other
- Study start
- 30 Aug 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obstructive sleep apnea (OSA), recognized as a highly prevalent sleep breathing disorder with severe complications, features a complex etiology. Poor understanding of disease pathogenesis limits the overall efficacy of interventions. Studies have found that upregulation of 5-HT7 expression in the lateral hypothalamus (LH) could reduce arousal threshold (ArTH) and induce an inhibitory effect to the respiratory central, which was associated with hypoxic stimulation. Therefore, the investigators speculate that the structural/functional abnormalities of the arousal-respiratory neural circuit, mediated by LH5-HT7, may play an important role in the pathogenesis of OSA. To verify the hypothesis, the investigators will compare the ArTH and the brain network presenting by multimodal MRI in normal individuals, snoring individuals, and OSA patients, to reveal the correlation between arousal dysregulation and the structure/function of LH regions; compare the changes of ArTH and brain network in OSA patients with low ArTH before and after CPAP treatment, to verify the interaction between hypoxia and arousal dysregulation, as well as whether the damaging performance of the arousal-respiratory brain regulation area in OSA patients can be partially reversed by relieving hypoxia. Above all, the joint application B team will further analyze the LH5-HT7 neural mechanism in the pathogenesis of OSA.
Detailed description
The study consists of two parts: The first part is a cross-sectional study comparing the differences in arousal threshold, loop gain, and the brain network structure and functional connectivity of the brain areas involved in micro-arousal-respiratory center regulation between the non-OSA group (including healthy individuals and those with simple snoring) and the OSA group; The second part is a cohort study, which conducts a three-month longitudinal follow-up of the OSA group to observe the changes in the indicators of the structure and function of the core brain areas related to ArTH and micro-arousal-respiratory center regulation after the correction of intermittent hypoxia through CPAP treatment.The specific research content is as follows:
- ArTH Comparative Analysis Based on Multimodal Assessment of OSA Etiology Select untreated OSA patients, simple snorers (with snoring symptoms, AHI < 5 events/h), and healthy individuals (without snoring symptoms, AHI < 5 events/h), matched for age and gender, and divide them into two groups.Non-OSA group (including healthy individuals and those with simple snoring) and OSA group . After all study participants have undergone upper airway CT, they are all subjected to overnight PSG with synchronous esophageal pressure monitoring, end-tidal carbon dioxide monitoring, and genioglossus electromyography (GGEMG) monitoring. A pharyngeal pressure regulation device is used to induce respiratory events with micro-arousals in the study participants under resistive ventilation, and the trends of ArTH, GGEMG, and respiratory drive (loop gain, LG) are analyzed among different sleep stages. Then, by integrating the above multimodal etiological parameters, the differences in micro-arousal regulation between OSA patients (high airway resistance and hypoxia group), simple snorers (high airway resistance without hypoxia group), and healthy individuals (low airway resistance without hypoxia group) are clarified. Furthermore, the weight of ArTH in the etiology of OSA is calculated, and the individual differences in ArTH among OSA patients and its correlation with the severity of the disease are analyzed.
- Feature Analysis of OSA Micro-arousal-Respiratory Central Regulation Network Based on Multimodal MRI By integrating multimodal MRI imaging data, including structural T1, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI), the differences in brain network structure and functional connectivity of brain regions involved in micro-arousal-respiratory central regulation between OSA patients, simple snorers, and healthy individuals with different ArTH levels are compared. This reveals the patterns of functional connectivity changes and structural basis related to micro-arousal abnormal regulation in OSA patients, and clarifies the correlation with the lateral hypothalamus (LH) brain region.
- Comparative Analysis of LH-Related Brain Region Structure and ArTH in OSA Patients with Low ArTH Before and After CPAP Treatment After OSA patients with different ArTH levels have undergone more than 6 months of CPAP treatment, ArTH and multimodal MRI imaging data (T1, DTI, rs-fMRI) are re-measured to observe the changes in ArTH and the structure/function of the core brain regions regulating micro-arousal-respiratory central in OSA patients after correcting intermittent hypoxia with CPAP treatment. These changes are compared with the ArTH and brain network structure of healthy controls to verify the damaging effects of hypoxia on brain networks and to clarify whether the damaging manifestations of the micro-arousal-respiratory central regulation regions in OSA patients can be partially reversed with treatment.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-OSA patients group | – | Diagnostic Test: MRIHealthy individuals (without snoring symptoms, AHI < 5 events/h)；Simple snorers (with snoring symptoms, AHI < 5 events/h) |
| OSA patients | – | Diagnostic Test: MRIPatients diagnosed with OSA |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Snoring Population: Individuals who regularly experience snoring during sleep, often resulting in loud and disruptive noises. Healthy Volunteer Population: Individuals characterized by the absence of sleep disorders or other health conditions that could affect sleep quality. These volunteers typically exhibit regular sleep patterns without snoring or sleep-disordered breathing and meet specific age and health criteria to ensure they represent a healthy comparison group. OSA (Obstructive Sleep Apnea) Patient Population: Patients diagnosed with OSA, a sleep disorder where the airway collapses or becomes blocked repeatedly during sleep.OSA is typically confirmed through an overnight sleep study that measures breathing interruptions and oxygen desaturation events.
Key inclusion criteria (12 listed)
- Age between 20 and 60 years.
- Symptoms of sleep snoring and daytime sleepiness.
- Confirmed diagnosis of OSA following overnight sleep monitoring.
- Age between 20 and 60 years.
- Symptoms of sleep snoring.
Key exclusion criteria (8 listed)
- Presence of severe pulmonary, neurological, or cardiovascular complications.
- History of long-term non-invasive positive pressure ventilation treatment (more than 3 months) or upper airway surgery.
- Sleep-disordered breathing due to special etiologies such as hypothyroidism, acromegaly, vocal cord paralysis, etc.
- Presence of severe mental illness, long-term alcohol abuse, or a history of prolonged use of sedative-hypnotic drugs.
- Central sleep apnea predominant sleep disorders due to various causes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIAlso: PSG, Genioglossus ElectromyographyMultimodal MRI technology is a method that combines various magnetic resonance imaging techniques, providing more comprehensive images and information about human tissues and organs. These different imaging techniques include, but are not limited to: Structural MRI (sMRI): Provides information about the types of brain tissues, such as gray matter, white matter, and cerebrospinal fluid. Functional MRI (fMRI): Dynamically measures the hemodynamic response related to brain neural activity, commonly used to study brain functional activities. Diffusion Tensor Imaging (DTI): Offers information on the structural connections between brain regions, which can be used to study the neural fiber pathways of the brain | Diagnostic test | Non-OSA patients group, OSA patients |
Primary outcome
Arousal threshold
Time frame: Three-month follow-up
Calculate the patient's arousal threshold based on PSG results.
Fractional anisotropy
Time frame: After three months of CPAP treatment, DTI were taken again on OSA patients to calculate the FA values.
The fractional anisotropy (FA) value, obtained through diffusion tensor imaging (DTI) measurements, was used to compare the brain functions between patients with obstructive sleep apnea (OSA) and those without. Additionally, a follow-up was conducted after three months of continuous positive airway pressure (CPAP) treatment for OSA patients to compare the FA values before and after treatment, thereby clarifying the changes in patients' brain functions.
Connectivity strength
Time frame: After three months of CPAP treatment, fMRI were taken again on OSA patients to calculate connectivity strength.
The investigators conducted functional MRI measurements on patients with obstructive sleep apnea (OSA) and non-OSA volunteers, calculated functional connectivity, and compared the differences in their results. Subsequently, the investigators followed up with the OSA patients who underwent three months of CPAP therapy and compared the functional connectivity of brain regions before and after treatment to clarify changes in patients' brain functions.
3 secondary outcomes
Sleep Stage Distribution
Time frame: Three-month follow-up
Apnea-Hypopnea Index
Time frame: Three-month follow-up
Oxygen Saturation
Time frame: Three-month follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2024.
- Individual participant dataSharing planned: Undecided. all IPD that underlie results in a publication
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A Study to Learn About the Monthly Dosing Study Medicine Called Berobenatide in Adults With Breathing Problems During Sleep and Overweight or Obesity Who Do Not Use a Breathing Machine (PAP) (VESPER-OSA 2)
Apnea, Sleep Disorders
Not yet recruitingPhase 2
Supplemental Oxygen for Sleep-Disordered Breathing in Adults With Chronic Opioid Use.
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Nightly Wearable Monitoring During Home-Based Submental Electrical Stimulation for Obstructive Sleep Apnea
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jingying Ye principal investigator
BeijingTsinghua Changgung Hospital，Tsinghua University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obstructive Sleep Apnea, run by Beijing Tsinghua Chang Gung Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yingqian Zhou (010-56119472, yingqianzhou9112@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arousal threshold (time frame: Three-month follow-up). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2024.