Pilot Funding

Associations Between Sleep & Disease Activity in Juvenile Idiopathic Arthritis 

Sarah Ringold, MD, MS

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic illness, the most common cause of acquired disability in children, and the sixth most common chronic childhood disease. Despite earlier disease recognition and expanded treatment options, children with JIA continue to report lower health-related quality life, increased fatigue, and increased sleep disturbances as compared to their healthy peers. The etiology of sleep disturbance and increased fatigue in JIA is not well-understood and their relationship to disease activity (e.g. inflammation) in unknown. In order to explore the associations among sleep, fatigue, and disease activity in JIA and to test the hypothesis that sleep disturbance and fatigue are manifestations of disease activity in JIA, we propose to collect data regarding sleep (actigraphy), disease activity (physician assessment, biomarkers), and patient and parent/proxy reports of fatigue and sleep, from a cohort of 20 children with polyarticular or extended oligoarticular JIA. We anticipate that the results of this pilot study will enable us to better understand the relationship between sleep disturbance, fatigue, and disease activity in JIA and, in doing so, will allow us to identify potential interventions that will result in improvement in both of these outcomes and also in health-related quality of life for children with JIA.

Transcriptional Effects of Sleep Disordered Breathing on Adipose Tissue

Sina Gharib, MD

Obstructive sleep apnea (OSA) is a prevalent disorder characterized by recurrent collapse of the upper airway during sleep leading to period of intermittent hypoxia and sleep-wake disturbances. OSA is associated with significant cardiovascular and neurocognitive morbidities, and has been recently linked to metabolic perturbations including insulin resistance, impaired glucose tolerance, and dyslipidemia. Obesity–a chronic illness of pandemic proportions, is one of the strongest risk factors for sleep apnea, yet the impact of OSA on adipose tissue biology is poorly understood. In this application, we intend to systematically explore the effects of sleep-wake disturbances (as manifested by OSA) on adipose tissue obtained from obese individuals. Our primary hypothesis is that OSA activates distinct transcriptional programs in adipocytes that mediate the metabolic and systemic disturbances observed in this disorder. To test our hypothesis, we will harvest subcutaneous and visceral fat from obese patients undergoing ventral hernia repair surgery. Participants will wear a home OSA monitor prior to surgery to determine sleep apnea severity. Whole genome expression profiling of adipose tissue will be performed followed by state-of-the-art computational analysis to determine biological pathways and genetic networks activated in adipocytes of obese subjects suffering from OSA.

Sleep-wake Disturbances in Adolescents Following Mild to Moderate Traumatic Brain Injury

See Wan Tham, MBBS

Traumatic brain injury (TBI) is a leading cause of disability in the United States, occurring frequently in the pediatric population with over 700,000 hospitalizations per year, and a peak incidence in adolescents. Sleep-wake disturbances have recently been recognized as common with 28% to 43% of samples reporting sleep problems up to six years post-injury. However, there are not yet data on the specific nature and diagnostic characteristics of these sleep-wake disturbances in the pediatric population. The aims of this application are to 1) characterize the type of sleep-wake disturbances experienced by adolescents with TBI, 2) identify clinical and behavioral risk factors for sleep disturbances, and 3) examine the relationship between sleep disturbances and daytime fatigue. A cohort of 60 adolescents, ages 12 to 18 years, with mild to moderate TBI within the prior 3 – 12 months will be recruited. Subjective and actigraphic assessment of sleep (10 days of recordings) will be conducted. Data from a same-age healthy cohort are available for comparison. This study will provide preliminary data for future investigations that may allow for the development of new interventions designed to decrease sleep disturbances in adolescents with TBI.

Brief Behavioral Therapy for Insomnia in Persons Living with HIV

Diana Taibi, PhD, RN

A large number (~73%) of persons living with HIV (PLWH) experience insomnia, which can result in reduced quality of life, non-adherence to HIV medications, and exacerbation of symptoms such as fatigue and depression. Despite such evidence, there is little research on interventions for insomnia in PLWH and no research on cognitive-behavioral therapy for insomnia (CBT-I), which is the standard of care for insomnia treatment in clinical sleep medicine. The purpose of the proposed study is to test the feasibility, acceptability, and initial efficacy of Brief Behavioral Treatment for Insomnia (BBTI), a short treatment based on the behavioral principles of CBT-I. One study has shown BBTI effective in older adults with insomnia, but the feasibility and efficacy in PLWH has not been studied. Sixty-four adults with HIV and chronic insomnia will be recruited from an urban clinic in western Washington. The study uses a wait-list control design.  The treatment group will receive the BBTI treatment, which involves four weekly 30-45 minute sessions (Sessions 1 and 3 in-person, Sessions 2 and 4 by phone). Feasibility outcomes will include participation, demonstrated behavior change (adherence to stable bedtime and rise time), and population-specific sleep factors. Acceptability of the treatment will be rated by participants. Sleep outcomes measured pre- and post-treatment will include insomnia symptoms (Insomnia Severity Index) and sleep efficiency (percentage of time in bed spent asleep) measured by seven days of sleep diaries and actigraphy (a wrist-worn activity sensor used to estimate wake and sleep). Findings from this study will support an NIH grant proposal for a randomized clinical trial of BBTI for PLWH.

Insomnia and Functional Recovery After Acute Lung Injury

Elizabeth Parsons, MD, MSc

Critical illness including acute lung injury is a life altering event, frequently associated with prolonged disability.  One potentially modifiable contributor to daytime impairment, sleep disturbance, has not been carefully studied in ICU survivors.  We have previously shown that, among ICU survivors requiring prolonged mechanical ventilation, insomnia symptoms in the first few months after discharge are independently associated with subsequent functional impairment (OR for independence in daily activities = 0.3, 95% CI: 0.2, 0.7). There remains a need to carefully characterize sleep wake abnormalities that underlie insomnia, and their clinical impact, in ICU survivors.

In this study, we will characterize the epidemiology of insomnia and identify its relationship to clinically relevant disability in a prospective cohort of 20 ALI survivors at Harborview Medical Center.  Using electronic medical record data abstraction, patient surveys, actigraphy, polysomnography, and neuropsychological standardized testing, we will identify modifiable ICU risk factors, sleep-wake abnormalities, and functional deficits associated with insomnia at 3 months post discharge.  Insights gained into the spectrum of sleep-wake abnormalities after critical illness may lead to the development of novel sleep-targeted therapies with potential to improve functional recovery.