Does Treating Obstructive Sleep Apnea in Obese Canadian Youth Improve Blood Sugar Control? (IMPACT Obesity)
|ClinicalTrials.gov Identifier: NCT01116375|
Recruitment Status : Unknown
Verified June 2011 by Katz, Sherri Lynne, M.D..
Recruitment status was: Recruiting
First Posted : May 5, 2010
Last Update Posted : June 16, 2011
|Condition or disease|
|Obesity Obstructive Sleep Apnea|
Rationale: The five-fold increase in prevalence of childhood obesity in Canada over the last 15 years has led to an increasing number of pediatric cases of obesity-related obstructive sleep apnea (OSA). Not only is the prevalence of OSA significantly higher among obese children compared with the general population, but in this group, routine treatment by adenotonsillectomy has a much lower cure rate. Instead, Positive Airway Pressure (PAP) treatment is usually prescribed. Other complications of obesity are also increasingly recognized in children, including metabolic disturbances with insulin resistance (IR). This is particularly concerning, since IR is an identified surrogate measure of future obesity-related sequelae, such as diabetes, dyslipidemia, cardiovascular disease (including hypertension, and heart rate disturbances), inflammation and impaired quality of life. Of particular interest, the IR related to obesity can be exacerbated by OSA and the severity of IR correlates with the severity of OSA. IR is measured using a homeostasis model assessment of insulin resistance (HOMA-IR) and is calculated from fasting blood glucose and insulin levels. In obese adults with OSA, HOMA-IR, as well as cardiovascular and other metabolic markers, has been shown to improve following PAP therapy. Such a study has not been done in children. We hypothesize that PAP treatment for obese children with moderate-severe OSA will improve markers of obesity-related disease.
Primary Objective: To determine whether, in obese children with moderate-severe OSA who are prescribed PAP therapy, increased hours of PAP usage per night over a one-year period is associated with a greater improvement in HOMA-IR. Secondary Objectives: To determine whether increased hours of PAP usage per night is associated with a greater improvement in the following outcomes: 1) sympathetic nervous system activation (systolic and diastolic hypertension, nocturnal hypertension, heart rate and heart rate variability); 2) inflammation 3) neurobehavioral and quality of life measures. Methods: Study design: prospective multi-centre cohort study. Study Population: Obese children (body mass index (BMI) ≥ 95th %ile for age and sex) 8-17 years old with moderate-severe OSA will be recruited for this study from four pediatric tertiary care centres across Canada. As per current standard of care, those children with moderate-severe OSA, defined as ≥ 10 obstructive events per hour on polysomnography, will be prescribed PAP treatment. Sample Size: We expect a medium effect size (0.5); therefore 10 subjects per parameter tested (n=4) in the regression model and 25% attrition requires the recruitment of 54 subjects. Measurements will be made at baseline and 12 months. Data collection will include HOMA-IR, 24-hr blood pressure measurements, electrocardiogram for heart rate and heart rate variability, C-reactive protein as a marker of inflammation, neurobehavioral/quality of life measures (Conners parent and teacher scales, Child Behavior Checklist and Pediatric Quality of Life Inventory) and physical activity questionnaire (Habitual Activity Estimation Scale (HAES)). Data Analysis: Multivariate linear regression analyses will be performed for our primary and secondary outcomes. Our dependent variable will be change in HOMA-IR; our primary independent variable will be average number of hours/night of PAP usage. Adjustment variables will be change in BMI %ile, pubertal stage (Tanner stage 1-2 vs.
3-5), and change in HAES. Similar analyses will be performed for our secondary outcomes.
Importance: Treatment of obesity-related OSA in adults has been shown to reduce morbidity and mortality. Our study is uniquely poised and timely, as it will be the first to examine the impact of PAP therapy in children on measures of insulin resistance and other obesity-related conditions. It will raise awareness of co-morbidities of obesity and OSA in childhood and support early intervention, before irreversible end-organ damage has occurred.
|Study Type :||Observational|
|Estimated Enrollment :||54 participants|
|Official Title:||Does Treating Obstructive Sleep Apnea in Obese Canadian Youth Improve Blood Sugar Control? A Multi-Centered Prospective Cohort Study|
|Study Start Date :||June 2010|
|Estimated Primary Completion Date :||June 2012|
|Estimated Study Completion Date :||September 2012|
Obese children with OSA
To determine whether, in obese children with moderate-severe OSA who are prescribed PAP therapy, increased hours of PAP usage per night over a one-year period is associated with a greater improvement in HOMA-IR
- HOMA-IR [ Time Frame: 1 year after start of PAP therapy ]Euglycemichyperinsulinemic clamp technique is the gold standard measurement technique for insulin resistance however, invasive and rarely used in clinical practice. A surrogate is the homeostasis model assessment (HOMA) formula for insulin resistance (HOMA-IR) Thus, lower HOMA values indicate higher insulin sensitivity. The estimate obtained with HOMA correlates well with measures of insulin resistance obtained from obese and non-obese children and adolescents with the clamp technique
- Systemic Hypertension [ Time Frame: 1 year after start of treatment with PAP ]Systemic hypertension,will be measured with 24-hour ABPM at baseline and 1 year. Summary measures for each of the day and night periods include average systolic and diastolic BP, and systolic and diastolic BP loads, as well as % nocturnal dipping. These summary measures have been shown to predict important outcomes including left ventricular hypertrophy, cardiovascular events, and death more accurately than casual BP measures
- Heart rate and heart rate variability [ Time Frame: 1 year after the start of PAP therapy ]Heart rate and heart rate variability will be analyzed from electrocardiography (EKG) data acquired during polysomnography performed at baseline and 1 year. EKG is more accurate than pulse oximetry to measure high- and low-frequency variability in heart rate and thus is the gold standard for obtaining these measures during sleep.We will focus on the RR interval as a measure of heart rate. Both time-domain components and frequency-domain components will be considered as measures of heart rate variability. We will use normative values as derived by Massin et al.
- hsCRP [ Time Frame: 1 year after start of PAP therapy ]Blood samples obtained at baseline, 6 months and 1 year will be assessed for levels of CRP, a protein which is released during the chronic inflammation underlying atherosclerosis. Compared with the standard CRP test, the hsCRP assay can detect lower protein concentrations with greater sensitivity and achieves better specificity for predicting vascular events
- Conners' Parent and Teacher Rating Scales [ Time Frame: 1 Year fter the start fo PAP therapy ]The Conners' Parent and Teacher Rating Scales have demonstrated excellent reliability and validity. These commonly used questionnaires rely on observer ratings to assess attention deficit/hyperactivity disorder (ADHD) and evaluate problem behaviour in children and adolescents. We will use the Revised Short version which contains 27 items with scales measuring oppositional behaviour, cognitive problems/inattention and symptoms of ADHD
- Child Behavior Checklist [ Time Frame: 1 year after start of PAPA therapy ]The Child Behavior Checklist is one of the most widely-used standardized measures in child psychology for evaluating maladaptive behavioural and emotional problems in children Specifically, this parent-report questionnaire contains 118 items aimed at assessing the frequency of observed internalizing (i.e. anxious, depressive, and overcontrolled) and externalizing (i.e. aggressive,hyperactive, noncompliant, and undercontrolled) behaviors.
- Pediatric Quality of Life Inventory (PEDS-QL) [ Time Frame: 1 Yaer after start of PAP therapy ]The PEDS-QL is a 23-item test designed to evaluate levels of functioning in 4 areas of health: physical, emotional, social and scholastic. This tool has demonstrated excellent reliability and validity and is frequently used to assess pediatric quality of life.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01116375
|Contact: Sherri L Katz, MD||613 737 7600 ext firstname.lastname@example.org|
|Contact: Lynda M Hoey, RN||613 737 7600 ext email@example.com|
|Alberta Children's Hospital||Recruiting|
|Calgary, Alberta, Canada|
|Contact: Valerie Kirk, MD|
|Stollery Children's Hospital||Recruiting|
|Edmonton, Alberta, Canada|
|Contact: Maisha Witmans, MD|
|Childrens Hospital of Eastern Ontario||Recruiting|
|Ottawa, Ontario, Canada|
|Contact: Sherri Katz, MD 613 737 7600 ext 2956 firstname.lastname@example.org|
|Montreal Childrens Hospital||Recruiting|
|Montreal, Quebec, Canada|
|Contact: Evelyn Constantin, MD|
|Principal Investigator:||Evelyn Constantin, MD||Montreal Children's Hospital of the MUHC|
|Principal Investigator:||Sherri L Katz, md||Childrens Hospital of Eatern Ontario|