Unveiling the Neural Mechanisms of 5-HT7 in Sleep Apnea Induced by Arousal Dysregulation

NCT06608888 | Recruiting

• 2 other identifiers: 23657-0-0182341247
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea; Arousal Dysregulation; Arousal Threshold; Lateral Hypothalamus; 5-HT7 Receptor

Outcome Measures

Primary Outcomes (3)

• Arousal threshold

  Calculate the patient's arousal threshold based on PSG results.

  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.

  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.

  After three months of CPAP treatment, fMRI were taken again on OSA patients to calculate connectivity strength.

Secondary Outcomes (3)

• Sleep Stage Distribution

  Three-month follow-up

• Apnea-Hypopnea Index

  Three-month follow-up

• Oxygen Saturation

  Three-month follow-up

Study Arms (2)

Non-OSA patients group

Healthy individuals (without snoring symptoms, AHI \< 5 events/h)；Simple snorers (with snoring symptoms, AHI \< 5 events/h)

Diagnostic Test: MRI

OSA patients

Patients diagnosed with OSA

Diagnostic Test: MRI

Interventions

MRI DIAGNOSTIC_TEST

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

Also known as: PSG, Genioglossus Electromyography

Non-OSA patients group; OSA patients

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tsinghua Chang Gung Hospital: lead

Study Sites (1)

No. 168 Litang Road, Changping District

Beijing, Beijing Municipality, 100028, China

RECRUITING

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Jingying Ye

  BeijingTsinghua Changgung Hospital，Tsinghua University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yingqian Zhou

CONTACT

010-56119472; yingqianzhou9112@126.com

Yue Yin

CONTACT

86 17600807298; yinyue1217@126.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of Otorhinolaryngology, Beijing Tsinghua Changgung Hospital.Professor of Tsinghua Medicine, Tsinghua University.

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 23, 2024
• Study Start: August 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 26, 2024

Record last verified: 2024-09

Locations

CN (1)