Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06608888
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-09-16
Brief Title:
Unveiling the Neural Mechanisms of 5-HT7 in Sleep Apnea Induced by Arousal Dysregulation
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Unveiling the Neural Mechanisms of 5-HT7 in Sleep Apnea Induced by Arousal Dysregulation
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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 structuralfunctional 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 structurefunction 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 treatmentThe specific research content is as follows
1 ArTH Comparative Analysis Based on Multimodal Assessment of OSA Etiology Select untreated OSA patients simple snorers with snoring symptoms AHI 5 eventsh and healthy individuals without snoring symptoms AHI 5 eventsh matched for age and gender and divide them into two groupsNon-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
2 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
3 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 structurefunction 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
1 ArTH Comparative Analysis Based on Multimodal Assessment of OSA Etiology Select untreated OSA patients simple snorers with snoring symptoms AHI 5 eventsh and healthy individuals without snoring symptoms AHI 5 eventsh matched for age and gender and divide them into two groupsNon-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
2 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
3 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 structurefunction 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None