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Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome (DYNAMIC)

Primary Purpose

Obstructive Sleep Apnea Syndrome, Gut Microbiota

Status

Withdrawn

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

CPAP or nasal dilators

About this trial

This is an interventional treatment trial for Obstructive Sleep Apnea Syndrome focused on measuring intermittent hypoxia, intestinal dysbiosis

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Sham Comparator

No Intervention

Arm Label

OSAS Patients treated with CPAP

OSAS Patients treated with nasal dilators

Non OSAS Patients

Arm Description

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

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

Non OSAS Patients will be the parallel control group

Outcomes

Primary Outcome Measures

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 )

Secondary Outcome Measures

Comparison of the intestinal microbiota between non-OSAS subjects and OSAS patients (before treatment with CPAP or nasal dilators)

Comparison of the diversity and composition of the microbiota (relative abundance of different phyla, genera, families, etc.) between the two groups (OSAS and non-OSAS).

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

Correlation between mean, systolic and diastolic 24 hours (day and night) arterial pressures, measured by 24-hours ambulatory recording, and modifications of the microbiota by OSAS and then by CPAP or nasal dilators

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

Correlation between changes in fasting blood glucose, glycated hemoglobin (HbA1c), total cholesterol, HDL-Cholesterol, LDL-Cholesterol, triglycerides and modifications of the microbiota by OSAS and then by CPAP or nasal dilators

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

Senescence markers, adipose RNA, cytokines, immunophenotyping of macrophages

Full Information

NCT ID

NCT04947410

First Posted

June 23, 2021

Last Updated

April 20, 2023

Sponsor

University Hospital, Grenoble

1. Study Identification

Unique Protocol Identification Number

NCT04947410

Brief Title

Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome

Acronym

DYNAMIC

Official Title

Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome : Impact of Continuous Positive Airway Pressure (CPAP) - A Randomized Controlled Trial Versus Nasal Dilators

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Withdrawn

Why Stopped

recruitment difficulty

Study Start Date

November 23, 2021 (Anticipated)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Grenoble

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

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. The data will be totally original in the field. The impact of this study can be major in allowing to propose pre/probiotics or drug treatments modulating intestinal dysbiosis during OSAS, combined or not with CPAP. Objective: The principal objective of the study is to compare gut microbiota changes (diversity and composition : relative abundance of different phyla, genera, families, alpha and beta diversity...) after 3 months of effective CPAP versus 3 months of placebo (nasal dilators), in patients with Obstructive Sleep Apnea Syndrome. The second objectives Methods : OSAS patients (with AHI > 30 / hour) will be screened in EFCR Service, Pneumology Department or Sleep Laboratory and proposed the study. If eligible they will be then followed over 3 months with 2 visits (inclusion visit at J0 and follow-up visit at 3 months). After the inclusion visit (J0) OSAS patients will be randomized for their treatment into "CPAP group" (effective CPAP treatment) or "nasal dilators group" (placebo treatment) for 3 months. The same assessments will be carried out at J0 and 3 months. Healthy volunteers (with no OSAS) will be the control group. They will be recruited by ad. They will carry out the assessments of inclusion visit (J0) only and compared then to the group of OSAS patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obstructive Sleep Apnea Syndrome, Gut Microbiota

Keywords

intermittent hypoxia, intestinal dysbiosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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)

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

OSAS Patients treated with CPAP

Arm Type

Active Comparator

Arm Description

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

Arm Title

OSAS Patients treated with nasal dilators

Arm Type

Sham Comparator

Arm Description

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

Arm Title

Non OSAS Patients

Arm Type

No Intervention

Arm Description

Non OSAS Patients will be the parallel control group

Intervention Type

Device

Intervention Name(s)

CPAP or nasal dilators

Intervention Description

CPAP = active comparator nasal dilators = placebo comparator

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Comparison of the intestinal microbiota between non-OSAS subjects and OSAS patients (before treatment with CPAP or nasal dilators)

Description

Comparison of the diversity and composition of the microbiota (relative abundance of different phyla, genera, families, etc.) between the two groups (OSAS and non-OSAS).

Time Frame

At inclusion visit (V1)

Title

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

Description

Time Frame

3 months

Title

Description

Time Frame

3 months

Title

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

Description

Senescence markers, adipose RNA, cytokines, immunophenotyping of macrophages

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean-Louis PEPIN, PhD

Organizational Affiliation

University Grenoble Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

Intestinal Dysbiosis During Obstructive Sleep Apnea Syndrome

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