Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome

NCT04947410 | Withdrawn DMC

• 1 other identifier: 38RC19.057
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Obstructive Sleep Apnea Syndrome; Gut Microbiota

Keywords

intermittent hypoxia; intestinal dysbiosis

Outcome Measures

Primary Outcomes (1)

• Diversity and composition of the microbiota (relative abundance of different phyla, genera, families, alpha (intra-sample) and beta (inter-sample) diversity ...)

  This analysis will compare changes in intestinal microbiota after 3 months of effective CPAP versus 3 months of placebo CPAP (sham-CPAP )

  3 months

Secondary Outcomes (4)

• 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

Study Arms (3)

OSAS Patients treated with CPAP

ACTIVE COMPARATOR

Patients with OSAS will have 1 in 2 chance of being randomized into "CPAP group"

Device: CPAP or nasal dilators

OSAS Patients treated with nasal dilators

SHAM COMPARATOR

Patients with OSAS will have 1 in 2 chance of being randomized into "nasal dilators group"

Device: CPAP or nasal dilators

Non OSAS Patients

NO INTERVENTION

Non OSAS Patients will be the parallel control group

Interventions

CPAP or nasal dilators DEVICE

CPAP = active comparator nasal dilators = placebo comparator

OSAS Patients treated with CPAP; OSAS Patients treated with nasal dilators

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)
• Patient likely, in the opinion of the investigator, not to be cooperative or respectful of the obligations inherent to participation in the study

Sponsors & Collaborators

• University Hospital, Grenoble: lead

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Jean-Louis PEPIN, PhD

  University Grenoble Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 interventional groups (15 OSAS patients into "CPAP group" versus 15 OSAS patients into "nasal dilators group") are evaluated in parallel against a control group (15 Non-OSAS Patients)

Study Record Dates

• First Submitted: June 23, 2021
• First Posted: July 1, 2021
• Study Start: November 23, 2021
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: April 24, 2023

Record last verified: 2023-04