Endothelial Dysfunction and Oxidative Stress in Children With Sleep Disordered Breathing.

NCT02247167 | Completed Phase 1 DMC

• 2 other identifiers: Sapienza-sdbC26A13W4AK
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Sleep disordered breathing (SDB) is a common disease in both adults and children and is caused by the obstruction of the upper airway during sleep. Unlike adults, most cases of paediatric SDB are due to the presence of enlarged tonsils and adenoids, thus the main treatment option is adenotonsillectomy (AT). It is well known that obstructive sleep apnoea (OSA) in adults increases the risk for hypertension, coronary artery disease and stroke, and there is now mounting evidence that SDB also has a significant impact on the cardiovascular system in children with reports of elevated blood pressure, endothelial dysfunction and altered autonomic cardiovascular control. Oxidative stress seems to play a pivotal role in impairing flow-mediated dilation (FMD) and consequently enhancing cardiovascular risk in SDB patients but the underlying mechanism is still undefined. Previously, we demonstrated that endothelial dysfunction is directly related to NADPH oxidase activation. Furthermore, recently we assessed the association between OSA, endothelial dysfunction and oxidative stress in adults showing that increased NADPH oxidase-generated oxidative stress and arterial dysfunction are partially reversed by nasal continuous positive airway pressure treatment. There is evidence in literature that cardiovascular morbidities associated with SDB are potentially reversible in children; AT may have a significant role in reversing the cardiovascular sequelae of SDB (e.g. children with OSA). Nowadays, there aren't studies that analyzed the role of NADPH oxidase-generated oxidative stress in SDB children. The purpose of the current research project is to examine the role of NADPH oxidase activity, oxidative stress, inflammation and endothelial function in SDB children, understanding the mechanisms involved in this disease. Furthermore we will analyse the effect of a AT on inflammation, oxidative stress, NADPH oxidase activity and endothelial function in SDB children.

Conditions

Obstructive Sleep Apnea of Child

Keywords

obstructive sleep apnoea, oxidative stress, FMD

Outcome Measures

Primary Outcomes (1)

• Assessment of flow mediated dilation (fmd)

  Baseline, week 4

Secondary Outcomes (1)

• Assessment of isoprostanes 8 Iso-pgf2alpha (pg/ml) levels

  Baseline, 4 weeks

Study Arms (1)

adenotonsillectomy (AT)

EXPERIMENTAL

Children with SDB studied before and after before adenotonsillectomy.

Procedure: adenotonsillectomy

Interventions

adenotonsillectomy PROCEDURE

adenotonsillectomy in children with OSAS and adenotonsillar hypertrophy.

adenotonsillectomy (AT)

Eligibility Criteria

• Age: 3 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children with diagnosed sleep breathing disorders

You may not qualify if:

• epilepsy
• acute or chronic cardiorespiratory or neuromuscular diseases
• chronic inflammatory diseases
• liver insufficiency
• serious renal disorders
• smoking
• vitamin assumption

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Sapienza University of Rome, I Clinica Medica, Research Tower

Rome, 00161, Italy

Location

Related Publications (4)

• Del Ben M, Fabiani M, Loffredo L, Polimeni L, Carnevale R, Baratta F, Brunori M, Albanese F, Augelletti T, Violi F, Angelico F. Oxidative stress mediated arterial dysfunction in patients with obstructive sleep apnoea and the effect of continuous positive airway pressure treatment. BMC Pulm Med. 2012 Jul 23;12:36. doi: 10.1186/1471-2466-12-36.

  PMID: 22824065 BACKGROUND

• Loffredo L, Martino F, Carnevale R, Pignatelli P, Catasca E, Perri L, Calabrese CM, Palumbo MM, Baratta F, Del Ben M, Angelico F, Violi F. Obesity and hypercholesterolemia are associated with NOX2 generated oxidative stress and arterial dysfunction. J Pediatr. 2012 Dec;161(6):1004-9. doi: 10.1016/j.jpeds.2012.05.042. Epub 2012 Jun 23.

  PMID: 22727869 BACKGROUND

• Violi F, Sanguigni V, Carnevale R, Plebani A, Rossi P, Finocchi A, Pignata C, De Mattia D, Martire B, Pietrogrande MC, Martino S, Gambineri E, Soresina AR, Pignatelli P, Martino F, Basili S, Loffredo L. Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation. 2009 Oct 20;120(16):1616-22. doi: 10.1161/CIRCULATIONAHA.109.877191. Epub 2009 Oct 5.

  PMID: 19805647 BACKGROUND

• Loffredo L, Zicari AM, Occasi F, Perri L, Carnevale R, Angelico F, Del Ben M, Martino F, Nocella C, Savastano V, Cesoni Marcelli A, Duse M, Violi F. Endothelial dysfunction and oxidative stress in children with sleep disordered breathing: role of NADPH oxidase. Atherosclerosis. 2015 May;240(1):222-7. doi: 10.1016/j.atherosclerosis.2015.03.024. Epub 2015 Mar 18.

  PMID: 25805361 DERIVED

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

• Francesco Violi, MD

  Sapienza University

  PRINCIPAL INVESTIGATOR

• Marzia Duse, MD

  Sapienza University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor of Internal Medicine

Study Record Dates

• First Submitted: July 9, 2014
• First Posted: September 23, 2014
• Study Start: February 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: July 1, 2014
• Last Updated: September 23, 2014

Record last verified: 2014-09

Locations

IT (1)