Extracellular microRNA: Biomarkers of Endothelial Dysfunction in Obese Adolescents & Adults With Obstructive Sleep Apnea

NCT ID: NCT03546751

Last Updated: 2018-06-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2024-12-31

Brief Summary

Using a prospective observational approach and a clinical trial design comparing the effectiveness of continuous positive airway pressure to diet and exercise, investigators plan to evaluate how obstructive sleep apnea (OSA) leads to endothelial dysfunction in adolescents and young adults and whether treatment of OSA can improve endothelial dysfunction. Concurrently, investigators will measure miR 92a/miR 210 levels in all subjects at baseline and following therapy to determine whether miR 92a/miR 210 levels reliably predict endothelial dysfunction in patients and responses to therapy.

Detailed Description

Investigators will randomize 100 OSA patients (age 13-21) to receive either continuous positive airway pressure (CPAP) plus baseline diet/exercise (n=50) or medical management (intensive diet and exercise; n=50). Only children in whom adenotonsillectomy is contraindicated (morbid obesity, history of adenotonsillectomy, lack of adenotonsillar hypertrophy) will be included. Investigators will conduct a randomized prospective comparative effectiveness study to assess the impact of treatment on OSA on endothelial function (peripheral arterial tonometry-EndoPAT). In addition to diagnostic polysomnography and EndoPAT at baseline, EV (extracellular vesicle) and non EV derived miR 92a/miR 210 concentrations, inflammatory cytokines concentrations, and body anthropometry will be measured. Following 3 mos of therapy and after 6mos of therapy, investigators will re-evaluate EndoPAT, EV and non EV derived miR 92a/miR 210 concentrations, inflammatory cytokines, and body anthropometry.

Throughout the study, investigators will maintain weekly telephone contact and monthly face-to-face visits as per standard of care in both groups to ensure ongoing success. In the medical management group (intensive diet and exercise), diet and exercise will be tracked by maintaining weekly telephone contact and monthly face-to-face visits with a registered dietician. For the CPAP group, investigators will also maintain weekly telephone contact and monthly face-to-face visits with a sleep technician to review mask fitting, and adherence reports, to optimize adherence to CPAP therapy.

Following completion at six months, polysomnography will be repeated.

Conditions

Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

CPAP

This arm will consist of patients with obstructive sleep apnea who will be asked to use CPAP nightly to treat their OSA for six months

Group Type: EXPERIMENTAL

Continuous Positive Airway Pressure

Intervention Type: DEVICE

This device delivers air pressure non invasively through a mask to stent open the upper airway to prevent obstruction during sleep. This is an FDA approved device that has been used for several decades to treat OSA.

Diet and Exercise

This arm will consist of patients with obstructive sleep apnea who will be asked to engage in dietary management and regular exercise for six months.

Group Type: ACTIVE_COMPARATOR

Diet And Exercise

Intervention Type: OTHER

This will consist of weekly telephone and monthly face to face visits to monitor and suggest measures to improve diet and regular exercise as conducted by a registered dietician.

Interventions

Continuous Positive Airway Pressure

This device delivers air pressure non invasively through a mask to stent open the upper airway to prevent obstruction during sleep. This is an FDA approved device that has been used for several decades to treat OSA.

Intervention Type: DEVICE

Diet And Exercise

This will consist of weekly telephone and monthly face to face visits to monitor and suggest measures to improve diet and regular exercise as conducted by a registered dietician.

Intervention Type: OTHER

Other Intervention Names

CPAP

Eligibility Criteria

Inclusion Criteria

• Otherwise healthy children and young adults with a diagnosis of obstructive sleep apnea based on polysomnography criteria of an obstructive apnea hypopnea index > 10 events/hr.
• For children a BMI range up to 99.7% and for adults BMI up to 32 kg/m2 is used.

Exclusion Criteria

• The presence of elevated blood pressure
• The presence of diabetes or pre-diabetes
• The presence of craniofacial anomalies
• The presence of neuromuscular disorders
• The presence of syndromic or defined genetic abnormalities
• Pregnancy
• History of smoking (any smoking within the prior 6 mos or >5 pack years total)
• The presence of infectious disease (e.g. including hepatitis B, C, HIV etc.)
• The presence of collagen vascular disease (e.g. lupus, arthritis, scleroderma, polymyositis, mixed-connective tissue disease, vasculitis etc)
• The presence of hepatic disease (including hepatitis fatty liver or cirrhosis)
• The presence of renal disease (including azotemia or clinical proteinuria)
• The presence of cardiopulmonary disease (e.g. known asthma, cystic fibrosis, congenital heart disease)
• Individuals using medications which could affect sleep or breathing (including hypnotics)
• Individuals using chronic anti-inflammatory therapy
• Individuals with any subjects with acute or chronic illness.
• Individuals using anti-hypertensive therapies
• Children with a a BMI > 99.7%
• Adults with a BMI > 32 kg/m2

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Rakesh Bhattacharjee

Associate Professor of Clinical Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Rakesh Bhattacharjee, MD

Role: CONTACT

rakesh@ucsd.edu

858-966-5846

References

Bhattacharjee R, Khalyfa A, Khalyfa AA, Mokhlesi B, Kheirandish-Gozal L, Almendros I, Peris E, Malhotra A, Gozal D. Exosomal Cargo Properties, Endothelial Function and Treatment of Obesity Hypoventilation Syndrome: A Proof of Concept Study. J Clin Sleep Med. 2018 May 15;14(5):797-807. doi: 10.5664/jcsm.7110.

Reference Type: BACKGROUND

PMID: 29734990 (View on PubMed)

Other Identifiers

170408

Identifier Type: -

Identifier Source: org_study_id