Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome : Impact of Continuous Positive Airway Pressure (CPAP) - A Randomized Controlled Trial Versus Nasal Dilators
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Diversity and composition of the microbiota (relative abundance of different phyla, genera, families, alpha (intra-sample) and beta (inter-sample) diversity ...)
研究概览
简要总结
Obstructive Sleep Apnea Syndrome (OSA) is one of the most common chronic diseases and is associated with prognostic cardiovascular and metabolic co-morbidities. OSAS is the recurrence of complete (apnea) or partial (hypopnea) collapse of the upper airway during sleep resulting in sleep fragmentation and chronic intermittent hypoxia (ICH) which are the major determinants of cardiovascular and metabolic complications including type 2 diabetes, obesity and non-alcoholic fatty liver. These comorbidities are associated with a change in intestinal microbial ecology. In most cases, there is a reduction in bacterial genetic diversity and more or less specific signatures of cardiovascular and metabolic diseases, making it possible to envisage personalized and innovative therapeutic treatments. In animals exposed to intermittent hypoxia, there is local hypoxia that increases intestinal permeability, produces a reduction in microbiota diversity and favors microbial species that are at the origin of pro-inflammatory factors. Continuous Positive Airway Pressure (CPAP) is the standard treatment for OSA. Its effect on the intestinal microbiota has not yet been evaluated.
详细描述
Background :
Obstructive Sleep Apnea Syndrome (OSAS) is one of the most common chronic diseases associated with cardiovascular and metabolic comorbidities (high blood pressure, type 2 diabetes, obesity and non-alcoholic fatty liver disease) that make it a prognosis.
These comorbidities are associated with a change in intestinal microbial ecology. In most cases, there is a reduction in bacterial genetic diversity and more or less specific signatures of cardiovascular and metabolic diseases which make it possible to envisage personalized and innovative therapeutic treatments.
In animals exposed to intermittent hypoxia, there is a local hypoxia that increases intestinal permeability, produces a reduction in microbial diversity, and favors microbial species that cause the secretion of pro-inflammatory factors.
Continuous Positive Airway Pressure (CPAP) is the gold standard for OSAS treatment. Its effect on the gut microbiota has never been evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-SAOS Group :
- •Men or women aged 18 to 70
- •Subject without any OSAS
- •Subject with Body Mass Index < 30 kg/m2
- •Subject who has given their free and informed consent in writing
- •Subject affiliated to the French social security system (or equivalent)
- •SAOS Group :
- •Men or women aged 18 to 70
- •Subject with OSAS (Apnea-hypopnea index > 30/hour)
- •Patient with CPAP indication and untreated at baseline
- •Subject with Body Mass Index < 30 kg/m2
- •Effective contraception for women of childbearing age (progestational or estrogen-progestin hormonal contraceptives (pill, ring, transdermal patch), intrauterine devices or definitive sterilization)
- •Subject who has given their free and informed consent in writing
- •Subject affiliated to the French social security system (or equivalent)
排除标准
- •Patient with resistant hypertension (PA ≥ 140/90 mmHg despite taking at least 3 drugs of different therapeutic classes at near maximal dose, including a diuretic)
- •Infection, progressive neoplasia, unstable cardiovascular pathologies, metabolic or intestinal pathologies
- •Taking of pre/probiotics and/or antibiotics in the 6 months prior to inclusion
- •Major sleepiness in at-risk populations for whom the introduction of treatment by CPAP equipment is mandatory and rapid (truck drivers, crane operators ...) according to the investigator
- •Patient with major desaturations during its polysomnographic diagnostic recording (≥ 2h with O2 saturation <90% on total sleep time)
- •Patient with high daytime sleepiness (Epworth score > 15)
- •Contraindication to the implementation of a CPAP treatment for the SAOS group
- •Contraindication to perform a subcutaneous biopsy (subject with hypersensitivity to a known local anaesthetic, abdominal skin lesion ...)
- •Drastic diet (vegetarian, vegan, pescetarian), food allergies
- •Subject referred to in Articles L1121-5 to L1121-8 of the CSP (pregnant woman, parturient, mother who is breast-feeding, person deprived of liberty by judicial or administrative decision, legally protected person)
- •Subject being in an exclusion period of another study or ongoing participation in a drug study
- •Patient likely, in the opinion of the investigator, not to be cooperative or respectful of the obligations inherent to participation in the study
结局指标
主要结局
Diversity and composition of the microbiota (relative abundance of different phyla, genera, families, alpha (intra-sample) and beta (inter-sample) diversity ...)
时间窗: 3 months
This analysis will compare changes in intestinal microbiota after 3 months of effective CPAP versus 3 months of placebo CPAP (sham-CPAP )
次要结局
- Comparison of the intestinal microbiota between non-OSAS subjects and OSAS patients (before treatment with CPAP or nasal dilators)(At inclusion visit (V1))
- Correlation between changes in arterial blood pressure and microbiota changes between OSAS and non-OSAS, and then between CPAP and nasal dilators, after 3 months of treatment only for OSAS patients(3 months)
- Correlation between changes in lipid and carbohydrate profiles and changes in microbiota between OSAS patients and non-OSAS subjects, then between CPAP and nasal dilators groups after 3 months of treatment(3 months)
- Comparison of markers of inflammation, senescence and remodeling of adipose tissue between OSAS and non-OSAS, and then between CPAP and nasal dilators after 3 months of treatment(3 months)