19/5000 (SYNAPSOT21) Predictive Factors of Sleep Apnea Syndrome in Down Syndrome (SYNAPSOT21)

• ClinicalTrials.gov Identifier: NCT03445962
• Recruitment Status: Unknown
• First Posted: February 26, 2018
• Last Update Posted: October 8, 2019
• Sponsor: University Hospital, Grenoble
• Information provided by (Responsible Party): University Hospital, Grenoble

Study Description

Brief Summary:

The obstructive sleep apnea syndrome (OSAS) is frequently reported in subjects with trisomy 21. The consequences of this syndrome are expressed in various disorders such as cognitive and cardiovascular alterations. It is also reported a premature exhaustion with the achievement of various professional or recreational activities, as well as an increase in the frequency of daytime sleepiness. In trisomy 21, there are factors that are systematically associated with obstructive apnea. The identification of these factors would make it possible to diagnose OSAS earlier, under-diagnosed in the population with trisomy 21 even though these OSAS are associated with increased cardiovascular risks.

The aim of this study is to identify the predictive factors associated with sleep apnea in the trisomy population in order to propose early detection.

OSAS treatment in a young adult with Down syndrome could reduce physical fatigue apparition during various activities, reduce daytime sleepiness, and have a positive impact on physical fitness, and therefore more broadly on health.

Condition or disease	Intervention/treatment
Down Syndrome; Sleep Apnea, Obstructive; Polysomnography	Diagnostic Test: Assessment of OSAS predictive factors

Detailed Description:

The predictive factors for OSA that will be studied are: physical activity level, dentofacial disharmonies, blood parameters, motor disabilities, heart rate variability parameters measured during sleep and during autonomic nervous stimulation by orthostatic test.

All these factors will be linked to the data obtained by:

1. polysomnography
2. by the joint use of seismocardiography

OSAS lead to many associated disorders, which identified early can be better supported to limit the deleterious effects of this OSAS:

(i) a sudden and repeated activation of the sympathetic nervous system triggered by sleep fragmentation (ii) intermittent hypoxia associated with OSAS may increase insulin resistance through the involvement of an inflammatory state and oxidative stress.

(iii) a significant level of diurnal fatigue limiting activities, thus promoting a sedentary lifestyle and increasing cardiovascular risk factors.

Several secondary objectives will therefore be studied:

1. Can OSAS be predicted by the existence of autonomic dysfunction?
2. Can OSAS be predicted by specific biological disturbances?
3. Can OSAS be predicted by the presence of a specific cranial structure?
4. Can OSAS be predicted by an insufficient level of physical activity?

Finally does the use seismocardiography make it possible to identify quickly and early these risk factors linked to OSAS?

Study Design

• Study Type: Observational
• Actual Enrollment: 40 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: SLEEP APNEA SYNDROME AND TRISOMY 21 : Exploration of the Predictive Factors in the Population With Trisomy 21
• Actual Study Start Date: November 15, 2017
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Groups and Cohorts

Group/Cohort

Intervention/treatment

Down Syndrome (DS); Assessment of OSAS predictive factors in Down Syndrome without or without OSAS

Diagnostic Test: Assessment of OSAS predictive factors; All subjects of the two groups realized the same assessment: Anthropometric evaluation; biological examination (hormonal, inflammatory and complete blood count, and lipidic profile); rest electrocardiogram; motor assessment (strenght, flexibility and balance); actigraphy; Autonomic nervous system assessment during sleep; Autonomic nervous system assessment during head up tilt test before and after physical exercise; maximal treadmill test (VO2 max measure); polysomnography; seismocardiography; questionnaires :sleep and physical activity

Outcome Measures

Primary Outcome Measures :

1. Identification of predictive factors associated to obstructive sleep apnea syndrome in DS subjects [ Time Frame: 4 months ]
   OSAS will be diagnosed with polysomnography and seismocardiography. AHI threshold will be 15 to diagnose an OSAS (score).

Secondary Outcome Measures :

1. dysautonomia role on OSAS in DS [ Time Frame: 1 day ]

   Cardiac response during exercise (existence of chronotropic incompetence

   %HR(reserve)lower than 80%)

2. Investigation of autonomic nervous system [ Time Frame: 1 day ]
   spectral variations of blood pressure and heart rate variability during head-up tilt test : (spectral density in ms² and normalized units)
3. Oxygenation and dysautonomia [ Time Frame: 1 day ]

   Cerebral and peripheral oxygenation parameters measured with near-infrared spectroscopy during head-up tilt test (delta Hbtot between supine and head up tilt positions)

   - Cardiac response during exercise (existence of chronotropic incompetence)

4. Investigation of dysautonomia during sleep [ Time Frame: 3 nignts ]
   spectral variations of heart rate variability (spectral density in ms² and normalized units)
5. Biological profile [ Time Frame: 1 day ]
   Disorders in blood parameters will be assessed by different inflammatory, corticotropic, thyroid and glycemic values in comparison with reference values.
6. anthropometric characteristics role on OSAS in DS [ Time Frame: 1 day ]

   Existence of morphologic specificities will be investigated:

   Craniofacial abnormalities with orthopantomogram (degree)

7. Metabolic syndrome [ Time Frame: 1 day ]

   Existence of morphologic specificities will be investigated:

   Neck, waist and hips circumferences (cm)

8. morphologic parameters [ Time Frame: 1 day ]

   Existence of morphologic specificities will be investigated:

   Body fat composition (%)

9. Quantification of physical activity [ Time Frame: 15 days ]
   Physical activity level will be assessed with actigraphy (min or h per day)
10. Motor skills [ Time Frame: 15 days ]
    motor capacities : strength (explosive leg power (cm) and handgrip measure), flexibility (cm), balance (cm)
11. questionnaire of physical activity [ Time Frame: 15 days ]
    G- PAQ and parental perceptions of physical activity (score)
12. Sleep questionnaire [ Time Frame: 15 days ]
    Epworth and Pittsburg questionnaire (score)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Adults with Down syndome voluntary to participated

Criteria

Inclusion Criteria:

Subjects with Down syndrome, able to practice physical activity all participants have received information all have signed the consent form

Exclusion Criteria:

• pregnant women
• Pharmacological treatment altering autonomic nervous system (ANS)
• Contra-indication to physical exercise, such as atlanto-axial instability

Contacts and Locations

Locations

France

CHU Grenoble Alpes

Échirolles, France, 38130

Sponsors and Collaborators

University Hospital, Grenoble

Investigators

• Principal Investigator: Stéphane DOUTRELEAU, MD; CHU Grenoble Alpes

More Information

Publications:

Leti T, Guinot M, Favre-Juvin A, Bricout VA. Difference of catecholamine responses to exercise in men with trisomy 21, with or without chronotropic incompetence. Physiol Behav. 2015 Apr 1;142:97-103. doi: 10.1016/j.physbeh.2015.02.007. Epub 2015 Feb 4.

Bricout VA, Guinot M, Faure P, Flore P, Eberhard Y, Garnier P, Juvin AF. Are hormonal responses to exercise in young men with Down's syndrome related to reduced endurance performance? J Neuroendocrinol. 2008 May;20(5):558-65. doi: 10.1111/j.1365-2826.2008.01695.x. Epub 2008 Mar 15.

Flore P, Bricout VA, van Biesen D, Guinot M, Laporte F, Pépin JL, Eberhard Y, Favre-Juvin A, Wuyam B, van de Vliet P, Faure P. Oxidative stress and metabolism at rest and during exercise in persons with Down syndrome. Eur J Cardiovasc Prev Rehabil. 2008 Feb;15(1):35-42. doi: 10.1097/HJR.0b013e3282f2bff3.

• Responsible Party: University Hospital, Grenoble
• ClinicalTrials.gov Identifier: NCT03445962
• Other Study ID Numbers: 38RC17.161
• First Posted: February 26, 2018
• Last Update Posted: October 8, 2019
• Last Verified: April 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Grenoble:

Autonomic nervous system; Heart rate variability; Physical Activity; exercise; biological parameters; cephalometry; body composition; actigraphy; motor capacity; physical fitness; aerobic capacity; seismocardiography

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Down Syndrome; Syndrome; Disease; Pathologic Processes; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn