Research on Pharmaceuticals for Children Awards – November 2009

NCRR awarded 18 grants to help determine outcome measures and increase the likelihood of success of future trials of treatments for children. The grants were awarded to 17 Clinical and Translational Science Award (CTSA) institutions to support 18 studies of pharmaceutical treatments for children. The CTSA consortium is a national network of 46 medical research institutions working together to improve the way biomedical research is conducted across the country. The $8.5 million in funding — administered by NCRR and provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development — will support studies which focus on three areas critical to health: pediatric cardiology, neonatology and pediatric neurology.

Albert Einstein College of Medicine

Bronx, N.Y.

Pediatric Hypertension Outcome Measures

Principal Investigator
Harry Shamoon, M.D.
E-mail: shamoon@aecom.yu.edu

Description:

The increase in the prevalence of pediatric hypertension (particularly that associated with being overweight or obese) is a major public health issue in the U.S., with African American and Latino youth disproportionately affected. The optimal treatment to prevent long-term consequences of these conditions remains to be characterized. Five CTSA institutions will examine the antecedents and prevention of adult cardiovascular disease in children and adolescents. The specific aims are: 1) to develop a multicenter and multidisciplinary consortium of investigators; 2) to conduct a cross-sectional study of cardiorenal and metabolic risk factors and biomarker profiles in pediatric essential hypertension; and 3) to conduct a pilot randomized clinical trial of a home-based lifestyle modification intervention. To address these aims, Albert Einstein College of Medicine will enroll ethnically diverse children between 10 and 18 years of age with pediatric hypertension at five CTSA sites. Patients will undergo baseline and 6-month examinations. Hypertensive children without left ventricular hypertrophy (LVH) will be randomized to a home-based intensive lifestyle modification or to a standard of care intervention (SCI). Patients with LVH will receive anti-hypertensive therapy and SCI follow-up. The study will evaluate the feasibility of enrolling and retaining patients during follow-up and will provide preliminary data on the efficacy of the intervention to justify the design and conduct of a larger, long-term clinical trial in this population.

Case Western Reserve University

Cleveland

Effect of BMI on Exposure-Response Relationships to Lisinopril in Children

Principal Investigator
Pamela B. Davis, M.D., Ph.D.
E-mail: pbd@cwru.edu

Description:

In children and adolescents, obesity creates high risk of hypertension (HTN) and its associated end-organ damage. In children and adolescents, the diagnosis of HTN by auscultatory means is subject to many confounders. Once a diagnosis is made, no treatment guidelines are available for drug selection or drug dosing for obese children and adolescents who may have altered drug disposition and response. This project will: 1) establish an approach to diagnosing HTN that does not suffer from the ambiguity of auscultatory approaches; 2) determine the impact of body mass index (BMI) on the exposure-response relationship of an anti-hypertensive agent already established as effective in a nonobese pediatric patient population; and 3) assess the impact on a biomarker for HTN-associated end-organ damage. The study will recruit children and adolescents of both sexes who are below 85th percentile, between 85th and 95th percentile and above 95th percentile for weight who are thought to have HTN based on auscultatory measurements. The diagnosis will be confirmed using innovative ambulatory blood pressure monitoring techniques. Each HTN patient will then undergo a novel, individualized dose escalation and exposure response study using lisinopril over eight weeks that will permit assessment of individual efficacy and safety while simultaneously allowing the assessment of the effect of BMI on drug disposition and response. The results will clarify diagnostic criteria for HTN and provide an important framework for assessing the impact of BMI on drug absorption, distribution, metabolism and excretion.

Case Western Reserve University

Cleveland

Methodological Improvement in Measuring Efficacy Outcomes in Antihypertensive Trials in Children

Principal Investigator
Pamela B. Davis, M.D., Ph.D.
E-mail: pbd@cwru.edu

Description:

The diagnosis and treatment of hypertension in children and adolescents remains a clinical challenge, because standard determinations of blood pressure (BP) in physicians' offices are subject to many confounding problems. This study will establish a new way to diagnose and assess the treatment of pediatric hypertension through the validation of an ambulatory blood pressure monitor (ABPM). Two specific aims are: 1) to validate the Spacelabs 90217 ABPM as a tool for accurately measuring BP in children, and 2) to analyze and model the patterns of ABPM observed over a 24-hour period in untreated hypertensive children in their ambient environment. To address the first aim, children of both sexes (n=120) in two age cohorts — six to 12 years and 12 to 18 years — will be enrolled at three participating centers. Trained observers will measure sequential BP in the same arm using an auscultatory device and the ABPM. The second aim will be accomplished through analysis of a data set already collected using the ABPM device. Software will be created to extract the raw data from the devices and demonstrate the ability to share this information across sites. The patterns observed over a 24-hour period in children with validated auscultatory blood pressure measurements above the 95th percentile for age and sex will be used to establish new, more objective criteria for the diagnosis of hypertension and to model patterns that may inform future therapeutic trials.

Columbia University

New York

Targets and Barriers for Hydroxyurea Therapy in Sickle Hemoglobinopathies

Principal Investigator
Henry Ginsberg, M.D.
E-mail: hng1@columbia.edu

Description:

Columbia University aims to create a five-site New York-Connecticut CTSA (NYCON) Pediatric Hemoglobinopathy Research Consortium to conduct four clinical/translational studies of hydroxyurea (HU) use in sickle-cell disease. The proposed studies focus on identifying novel indications for HU, pharmaco-genomic prediction of response and risks of and barriers to its use. Each of the four studies will be open to multi-site enrollment. A common database and DNA repository will be created, using existing protocols and procedures, informed consent, assent and other requisite study documents. The university will recruit more than 1,200 patients while building its capacity for clinical and translational research as well as increasing training opportunities. The project will: 1) develop an enduring infrastructure across the participating CTSA sites to support studies of HU use in children with sickle-cell disease, including developing standardized study design and recruitment protocols, shared consent and assent forms, a common biomarkers database and a shared DNA repository; and 2) enhance four existing sickle-cell studies by expanding recruitment across these five CTSA sites.

Duke University

Durham, N.C.

Development of a Pharmacokinetic Algorithm to Improve Outcomes in Neonates

Principal Investigator
Robert M. Califf, M.D.
E-mail: calif001@mc.duke.edu

Description:

Appropriate dosing of most products given to neonates is unknown, and extrapolation of pharmacokinetic (PK) data obtained from older children and adults has often failed to accurately predict premature infant drug disposition. Neonates are, therefore, at high risk of adverse drug reactions and therapeutic failure. Conducting PK trials in critically ill neonates is limited by risk associated with blood loss related to study procedures, the need to minimize the frequency of needle sticks and poor consent due to parental and provider concern. This research will develop and validate a PK algorithm that will use minimal and opportunistic sampling of blood and other body fluids. This algorithm can then be used as a platform for subsequent PK studies. The algorithm will be developed and refined using samples obtained from ongoing and completed neonatal PK trials of antimicrobial agents — including the BPCA sponsored meropenem trial. The algorithm will be validated prospectively to predict the accuracy of venipuncture-free components (urine, saliva, endotracheal tube or scavenged blood) in describing the PK of piperacillin/tazobactam. The clinical validation study will enroll 32 infants at five sites.

Indiana University School of Medicine

Indianapolis

Clinical and Genetic Predictors of Vincristine-Induced Peripheral Neuropathy

Principal Investigator
Anantha Shekhar, M.D., Ph.D.
E-mail: ashekhar@iupui.edu

Description:

Vincristine is among the most commonly used anticancer agents, but little is known about its therapeutic dosing. Suboptimal vincristine dosing can lead to peripheral neuropathy (PN) due to drug overdosing or lack of efficacy due to subtherapeutic dosing. This research will stimulate collaborative multidisciplinary, basic and clinical science focused on developing clinical and nonclinical outcome measures that can be used to guide and optimize vincristine dosing in ways that will minimize vincristine-associated PN and improve efficacy in children with acute lymphoblastic leukemia (ALL). The study will test the clinimetric properties of several pediatric PN clinical measurement approaches and evaluate the data for pharmacogenetic predictors of vincristine-associated PN. Because preliminary data support a strong association between PN severity and vincristine metabolizing enzyme (cytochrome P450 3A5) genotype, the project will explore the relationship between pharmacogenetic biomarkers of vincristine PN and clinical measures. The study will also evaluate the association of pharmacogenetic polymorphisms in the vinca alkaloid pharmacologic pathway with vincristine PN. Children with precursor B cell ALL (n=110) will be enrolled in a multicenter prospective clinical trial involving a consortium of four leading academic medical centers, three of which are CTSA sites. DNA will be collected for genotyping and patients will be followed for evidence of vincristine PN using multiple noninvasive assessment tools.

Stanford University

Palo Alto, Calif.

Methadone vs. Morphine PK/PD in infants and young children after cardiac surgery

Principal Investigator
Harry B. Greenberg, M.D.
E-mail: harry.greenberg@stanford.edu

Description:

The use of methadone to provide analgesia may be increasing due to advantages compared to other commonly used opioid analgesic drugs. However, there is a paucity of information in neonates and infants. In this population, fentanyl and morphine are most commonly used for opioid analgesia following major surgery, but methadone may offer superior efficacy with fewer side effects. The project will study the pharmacokinetics (PK) and pharmacodynamics (PD) of methadone in neonates and infants in the intensive care unit, following cardiac surgery. Subjects will receive intravenous methadone or morphine (“study drug”) delivered by an initial IV injection followed by a nurse-administered patient-controlled analgesia (PCA) device for postoperative pain for 24 hours. Subjects will also receive lorazepam as needed for agitation as indicated by specific criteria. The study drug will be discontinued after 24 hours to facilitate “wash out” sampling and determination of elimination half-life. Beginning at 24 hours, fentanyl will be used for analgesia at an equianalgesic dose to be determined by the investigator based upon the current PCA study drug dose. Subjects will be monitored for temperature (rectal, skin), electrocardiogram, heart rate, systemic arterial blood pressure, central venous blood pressure, respiratory rate, oxygen saturation (pulse oximetry), near-infrared spectroscopy (head, lower body) and urine output.

Tufts University

Boston

Improving BPD Predictors and Outcomes for Clinical Trials

Principal Investigator
Harry Selker, M.D., M.S.P.H.
E-mail: harry.selker@tufts.edu

Description:

Multiple studies have attempted to define a constellation of signs and symptoms in high-risk newborns to accurately define bronchopulmonary dysplasia (BPD) and to predict the subsequent development of chronic respiratory morbidity (CRM) including asthma, repeated respiratory infections, re-hospitalizations and abnormalities on pulmonary function testing. While intratracheal administration of recombinant human superoxide dismutase to premature infants at birth did not prevent BPD, treated infants had a 55 percent reduction in CRM - compared to placebo controls at one year corrected age. This suggests that current definitions of BPD are unreliable predictors of CRM, and a more robust outcome is needed to evaluate potential therapies. The project will undertake a prospective, longitudinal observational study in 85 preterm infants born at 24 to 29 weeks gestation enrolled at four CTSA sites and an additional site in London. Evaluations of early clinical assessments will be performed along with analysis of potential biomarkers of oxidation, inflammation and genetic predisposition for lung injury in the maternal placenta, as well as from blood, urine and tracheal aspirates from the infants. Data will be correlated with indicators of CRM at six months corrected gestational age. Pulmonary function testing, respiratory diaries and pulmonary questionnaires will be used to define CRM and establish more predictive variables for future clinical trials. Enhanced follow-up will use cell phones to permit close contact between the parents and study team to ensure that longer-term outcome variables are collected.

University of Alabama at Birmingham

Birmingham, Ala.

Nasal Potential Difference Studies Utilizing CFTR Modulators

Principal Investigator
Lisa M. Guay-Woodford, M.D.
E-mail: lgw@uab.edu

Description:

Phase II clinical trials have demonstrated proof of concept that small-molecule potentiators of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function can improve measures of CFTR activity and lung function in cystic fibrosis (CF) patients expressing G551 D CFTR, a CF mutation resident at the cell surface. This approach may also apply to AF508 CFTR, if sufficient protein resides in the plasma membrane, thus representing a potential treatment for a large majority of CF patients. However, many consider this concept to be controversial due to conflicting reports and the lack of sensitive assays of AF508 CFTR activity in vivo. The nasal potential difference (NPD) is a well-established bioelectric assay of CFTR function but has been hampered by poor standardization between sites. An international effort to standardize the NPD measurement significantly improved performance and sensitivity of the assay. The naturally occurring flavonoid quercetin strongly activates wild-type CFTR in vitro and in vivo (by NPD), and AF508 CFTR redirected to the plasma membrane in cell culture. The biomarker development study will leverage the NPD assay by testing whether a CFTR potentiator (quercetin) can detect surface CFTR activity in AF508 homozygous individuals, thus identifying candidates for systemic CFTR potentiator therapy. The project will also compare results of ion transport measurements made using AF508 homozygous cells. Results will help determine the potential of using this biomarker in trials examining other systemic CFTR modulators intended to address the basic CF defect.

University of California at Davis

Davis, Calif.

A Toolbox of Outcome Measures for Targeted Treatment Trials in Children

Principal Investigator
Lars F. Berglund, M.D., Ph.D.
E-mail: lars.berglund@ucdmc.ucdavis.edu

Description:

The project's goal is to create a toolbox of quantitative measures for use in targeted treatment trials for neurodevelopmental disorders in children. The grant focuses on fragile X syndrome (FXS), the most common cause of inherited intellectual disability, as a model condition, but the toolbox may be applicable to a variety of conditions. The first aim is to demonstrate feasibility, reliability and utility of outcome measures for clinical trials of 50 children with FXS (versus 50 controls), including prepulse inhibition (sensorimotor gating), standardized cognitive tests, face processing (social behavior/cognition), visual processing (contrast detection paradigms) using infrared eye-tracking technology, continuous performance tests (attention and inhibition) and an event-related brain activity measure (sensory processing and cognitive functioning). The second aim is to work closely with multiple CTSA sites that link with the National Fragile X Foundation's Fragile X Clinical and Research Consortium in two training workshops on using these measures in targeted treatment trials in FXS. Finally, the project will develop database and data collection standards for the toolbox, including a relational database for data storage and retrieval and a Web-based interface for sharing data across collaborating sites. Additionally, this toolbox effort can serve as a companion effort to the NIH Toolbox of Assessment of Neurological and Behavioral Function currently being developed under the NIH Blueprint for Neuroscience Research.

University of Colorado Denver

Aurora, Colo.

Development of a Small Volume Sampling Technique for Fentanyl Pharmacokinetic, Pharmacodynamic and Pharmacogenetic Analysis in Preterm and Term Neonates With and Without Cyanotic Congenital Heart Disease

Principal Investigator
Ronald J. Sokol, M.D.
E-mail: sokol.ronald@tchden.org

Description:

Neonates are considered "therapeutic orphans" for almost all currently available drugs. Without available analytic techniques to effectively examine pharmacokinetic levels of parent drugs and metabolites, it is impossible to make meaningful conclusions about drug distribution and potential toxicities. Pharmacokinetic (PK), pharmacodynamic (PD) and pharmacogenetic (PG) studies in infants, especially neonates, have been extremely challenging secondary to the difficulties involved in obtaining adequate sample size and necessary blood volumes for analysis and considering patient safety. This project will: 1) design a platform strategy to evaluate PK, PD and PG in preterm and term neonates, with and without cyanotic congenital heart disease; and 2) build a clinical trials network to systematically study the PK, PD and PG of drugs in preterm and term neonates. A multicenter, in-patient study will evaluate the PK, PD and PG of a continuous infusion of fentanyl in preterm and term neonates. The project will test the hypothesis that the PK and the metabolism of fentanyl, a representative probe for cytochrome 3A4 substrates, is different in infants compared to children or adults and will have different PD correlates. This study will use a novel small-volume analysis that will allow frequent sampling using extremely small amounts of blood. Additionally, it will correlate results with an observational pain scale, physiologic measurements and genetic polymorphisms.

University of Michigan at Ann Arbor

Ann Arbor, Mich.

Pediatric Cardiac Intensive Care Research Consortium and Data Standards Repository

Principal Investigator
Kenneth J. Pienta, M.D.
E-mail: kpienta@umich.edu

Description:

Fatality rates among infants and older children with complex congenital and acquired heart disease (CHD) have improved dramatically in the past two decades. Clinicians are increasingly focused on reducing treatment morbidity and improving outcomes related to functional impairments and quality of life. A critical need exists to conduct high-quality clinical research on predictors and causes of poor outcomes in CHD. Single-institution studies are of limited benefit due to the relative rarity of any specific CHD lesion, the diversity and evolution of treatment options and, importantly, variability across centers in the type and quality of perioperative data collected. The lack of sound evidence defining relevant measures of outcome further complicates clinical research. Thus, consensus and standardization are needed for multicenter collection of specific clinical data variables that will better define morbidity and serve as proximal outcome markers of effectiveness for drug trials and other interventions. The project will develop a shared infrastructure through a coalition of pediatric cardiac intensive care units (PCICU) to directly address these needs. The specific aim is to develop a consortium of dedicated PCICUs led by CTSA-supported institutions and to systematically collect perioperative clinical data to identify robust clinical outcome measures. The measures developed and data collected from this effort will facilitate multicenter drug and intervention studies and studies of longer-term outcomes in children who are treated for CHD.

University of North Carolina

Chapel Hill, N.C.

Improving Outcome Measures for Chronic Lung Disease of Prematurity

Principal Investigator
Etta D. Pisano, M.D.
E-mail: etpisano@med.unc.edu

Description:

Many of the therapies used to treat premature infants have never been tested in this population, or they are of questionable efficacy — in part because of inadequate outcome measures. This is true of chronic lung disease (CLD), a primary or secondary outcome for the efficacy of many treatments used on premature infants. Current tools for assessing CLD rely on oxygen dependence, a gross measure of a single aspect of the severity of disease, and do not capture the nuances of the functional limitations related to lung pathology in premature infants. The goal of this project is to develop a robust, reliable and precise bedside measurement tool for assessing CLD severity in premature infants based on functional, patient-related outcomes. The project will generate a list of potential measurement tool assessment items by interviewing experienced clinical specialists, parents and national experts in the field. Items will address functional domains such as feeding, transition, handling and sleep. Tool items and outcome scales will be selected, operationalized and tested, using an adaptation of the Patient-Reported Outcomes Measurement Information System (PROMIS) — including structured cognitive interviews, user focus groups and feedback from individual users. The project will field-test the refined tool at five collaborative sites with 150 infants at 36 weeks corrected age, and will then subject the tool to standard reliability and validity tests of its results. Current NIH definitions of CLD will provide another source of construct validity testing.

University of Pittsburgh

Pittsburgh

Cardiac Outcome Measures for Pediatric Muscular Dystrophy Research

Principal Investigator
Steven Reis, M.D.
E-mail: sreis@pitt.edu

Description:

Cardiomyopathy — a cause of morbidity and mortality in muscular dystrophy patients — is attaining increasing levels of significance due to improvements in pulmonary and nutritional support for muscular dystrophy patients. However, there is little experience with multicenter drug trials to treat or prevent the cardiac complications of muscular dystrophy, reflecting a dearth of experience with sensitive and reliable measures to determine cardiac outcomes of interventions. This study will develop cardiac outcome measures that can be reliably implemented across a consortium of clinical sites devoted to the study of pharmaceutical treatments for muscular dystrophy. The project will: 1) train personnel and establish standardized protocols in muscular dystrophy patients, ages eight to 18 years, for specified echocardiographic measurements; 2) perform a cross-sectional study collecting echocardiographic data on muscular dystrophy patients, ages eight to 18 years, to determine sensitive indicators of cardiac dysfunction in this clinical population; and 3) establish a protocol for cardiovascular magnetic resonance for the same clinical cohort in two clinical trial sites and compare pilot data with echocardiographic data.

University of Texas Health Science Center at Houston

Houston

Advanced MRI to Assess Neonatal Care and Outcome

Principal Investigator
David D. McPherson, M.D.
E-mail: David.d.McPherson@uth.tmc.edu

Description:

In neonatology, crucial neurosensory impairments (NSI) are not apparent until at least two years of age. Recent advances in magnetic resonance imaging (MRI) have dramatically improved the speed and efficiency of neurological disease trials in adults. But safely performing and reliably assessing MRI in very premature infants has been challenging. A cohort study — funded through a CTSA Pilot Award — is addressing this gap by evaluating the relationship between neonatal care, advanced MRI measures of brain injury and NSI. The ultimate goals of the pilot cohort study and this supplement grant project are to accelerate drug discovery by identifying promising imaging biomarkers of neonatal care and neurological outcomes. Specifically, this project aims to: 1) perform robust post-image processing for diffusion tensor tractography (DTT) and magnetic resonance spectroscopy (MRS) in 70 very preterm infants (using data already collected from the CTSA pilot cohort study); 2) identify sensitive DTT and MRS measures that correlate significantly with neonatal insults and development of NSI; and 3) perform a two-center prospective cohort study, with the University of Texas Medical Branch at Galveston, to validate promising hypotheses and establish standardized MRI acquisition methods for multicenter trials in children. Fifty very preterm infants will be prospectively enrolled within a six-month period.

University of Utah

Salt Lake City

Improving Pediatric Outcomes Through Cost-Effective Management of the Neonatal Abstinence Syndrome

Principal Investigator
Donald McClain, M.D., Ph.D.
E-mail: donald.mcclain@hsc.utah.edu

Description:

Neonatal abstinence syndrome (NAS) following maternal treatment with narcotics during pregnancy is an increasing problem worldwide that often requires treatment of newborns with narcotics. Newborn pain is often also treated with opioids. Methadone is used in both cases but without pharmacologic data in newborns. In this study, methadone enantiomer-specific kinetics, cardiac effects, bioavailability and pharmacogenetic factors related to kinetics will be studied in neonates in the neonatal intensive care unit (NICU). The project will also determine the frequency, costs of care, length of hospital stay and variation in management of NAS at birth through 18 months of age. Detailed clinical data will be extracted from chart reviews of patients with NAS. These will be complemented with a review of a large electronically linked database that includes data from 32,511 births in 2007, resulting in one of the largest samples of patients with NAS that has been reported. Preliminary studies in older children suggest that the dosing pattern of methadone will need to be altered to reduce the likelihood of reaching toxic levels. These data will provide evidence-based dosing guidelines for methadone use in a prospective study of treating NAS with morphine and phenobarbital (alone or in combination). They will also provide dosing information to guide the use of methadone for analgesia in neonates in the NICU.

University of Washington

Seattle

Advancing Patient Reported Outcomes in children with Cystic Fibrosis

Principal Investigator
Mary L. Disis, M.D.
E-mail: ndisis@u.washington.edu

Description:

Patient-reported outcome measures (PROs) and measures of the patient's actual performance of tasks on tests have become increasingly important measures of efficacy for evaluating treatment benefit. There is currently no PRO for evaluating outcomes in cystic fibrosis (CF) that has been approved by the FDA. This lack of an acceptable instrument poses significant limitations on sponsors for obtaining approval of disease-altering therapies that are currently in human trials. A promising experimental PRO measures symptoms and impacts of pulmonary exacerbations in adults and adolescents with CF. This project will transition this PRO and a complementary breathing test (performance measurement) into the younger pediatric population. The primary goal is to assess the ability to detect change (effect sizes) and key components of validity (known groups and construct) of the PRO (CF Respiratory Symptom Diary) and the performance measure (the Single Breath Ease of Breathing Scale) in pediatric patients with CF experiencing an exacerbation in pulmonary symptoms before and after receiving antibiotic therapy. The study will also compile a detailed document (a user manual), outlining all necessary components for the efficient development of PROs and performance measures with a focus on respiratory symptoms for pediatric population.

Vanderbilt University

Nashville, Tenn.

Measuring Sleep in Autism: Use of Wireless, Comfortable, and Home-Based Tools

Principal Investigator
Gordon R. Bernard, M.D.
E-mail: gordon.bernard@vanderbilt.edu

Description:

Pediatric insomnia, defined as difficulty initiating or maintaining sleep, affects one to six percent of children in the general population and 50 to 75 percent of children with neurodevelopmental or psychiatric comorbidities. Effective treatments, whether pharmacologic, behavioral or both, represent an opportunity to improve sleep and also daytime functioning of the child and family. To carry out pediatric insomnia trials, however, it is critical to establish well-defined and effective outcome measures. Polysomnography (PSG) is cumbersome, laboratory-based, high-cost and not universally tolerated, especially by children with tactile sensitivities or anxiety. Vanderbilt University will develop wireless, comfortable, home-based and low-cost tools to measure sleep patterns in pediatric studies. Researchers are specifically focusing on well-characterized children with autism spectrum disorders (ASDs). In this multicenter study, 60 children (40 with ASD, 20 typically developing) - ages four to10 years - will undergo simultaneous monitoring with PSG, actigraphy and electrodermal activity (EDA) sensors, and also wear the actigraphy and EDA sensors for two weeks. The university will define the role of these novel sensors as outcome measures of sleep patterns and relate our findings to parental concerns about insomnia. The findings will provide the foundation for future interventional studies in which actigraphy and EDA can serve as nonintrusive and low-cost measures of improvement in sleep and daytime functioning.