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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03922165
Other study ID # 18-015848
Secondary ID
Status Completed
Phase
First received
Last updated
Start date May 22, 2019
Est. completion date December 31, 2021

Study information

Verified date March 2022
Source Brigham and Women's Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

The purpose of this multi-center observational study (utilizing the sites enrolling patients for the Pediatric Adenotonsillectomy Trial for Snoring (PATS) [1U011HL125307-O1A1]) is to gather data regarding children with Down syndrome (DS) and Sleep Disordered Breathing (SDB) referred for treatment with adenotonsillectomy to inform a future randomized controlled trial in this population.


Description:

Down syndrome (DS) is associated with a wide range of neurobehavioral and physical morbidities. Obstructive sleep apnea (OSA) is prevalent in children with DS and causes a myriad of physiological stresses that may exacerbate neurobehavioral and cardiac morbidities. Improving sleep health thus provides a modifiable intervention target for improving behavior, cognition, quality of life, and physical health of children with DS. However, critical knowledge gaps limit the adoption and implementation of effective OSA interventions, resulting in practice variability and suboptimal treatment of OSA across the spectrum of DS. In particular, it is in unclear how to select candidates likely to benefit from adenotonsillectomy (AT) and how to utilize information from polysomnographic, clinical, and demographic parameters to predict children most likely to benefit from AT compared to alternative treatments or to watchful waiting. The goal of this study is to collect the necessary data to plan and execute a future pivotal RCT of the role of OSA treatment in the care of children with DS. This study will provide critical information on the methodological approaches for conducting such a randomized controlled clinical trial (RCT), informing the appropriate recruitment strategies, patient population and outcome measures for a future clinical trial. The investigators will leverage expertise in pediatric sleep medicine, clinical trials, neuropsychology, and DS as well as the PATS clinical trials infrastructure to catalyze a new DS clinical research initiative. Our proposed next steps are to enroll in an observational study at active PATS centers 50 children with DS who are referred for clinically indicated evaluation and treatment of OSA. At baseline and 6 months following AT, these children will undergo systematic assessments of sleep, behavior, cognition, daytime functioning, and quality of life, generating key data to inform the design of a later pivotal RCT. Healthy Sleep for Children with Down Syndrome (HELP-DS) intends to take advantage of a successful collaboration of leaders in sleep medicine, otolaryngology and clinical trials to efficiently leverage experiences from the The Childhood Adenotonsillectomy Trial (CHAT) as well as the current resources of the PATS trial to collect data for the evaluation of key questions needed to design a future RCT, including approaches related to the selection of participating sites, the patient population to receive the intervention, and outcome measurements. The primary objective of HELP-DS to determine the feasibility of recruiting and retaining individuals in an observational study of AT across multiple clinical sites. Secondary objectives are: 1. Evaluate the feasibility of collecting a range of baseline and outcome data, and specifically the ability of children to perform neurobehavioral assessments (GoNoGo, pegboard task). 2. Understand issues related to patient preference, equipoise, and barriers to treatment. The investigators will track how many children referred for AT actually undergo surgery, the time interval between referral and surgery, other interventions pursued, and factors such as insurance, socio-economic factors, and cultural norms, that associate with family-decision making. 3. Examine the consistency and completeness of Healthcare Utilization (HCU) data extracted across our sites, describing differences by recruitment site, health, system characteristics, insurance-related factors, etc. The investigators will estimate incidence rates of HCU events for hospital admissions, emergency department/unscheduled office visits, specialty consultations and medication use during the 6 months following surgery and compare rates to those for the year prior to surgery. These aims have substantial public health significance given the high morbidity of Down syndrome and sleep-disordered breathing in children.


Recruitment information / eligibility

Status Completed
Enrollment 26
Est. completion date December 31, 2021
Est. primary completion date December 20, 2021
Accepts healthy volunteers No
Gender All
Age group 3 Years to 13 Years
Eligibility Inclusion Criteria: - DS diagnosis regardless of genetic status (e.g., mosaicism or translocation). - Aged >3 to <13 years at the date of consent. - Primary indication for AT is nocturnal obstructive symptoms (i.e., not recurrent infections or other indications). - Deemed to be a candidate for AT by Ear, Nose and Throat (ENT) evaluation; that is, no technical issues that would be a contraindication for surgery such as submucous cleft palate. Exclusion Criteria: - Prior tonsillectomy (partial or complete). - Severe chronic health conditions that would contradict surgery (severe morbid obesity, unrepaired cyanotic congenital heart disease, bleeding disorders). - Severe behavioral problems that would preclude participation in the study's testing procedures (PSG, actigraphy). - Severe OSA with respiratory failure needing urgent/emergent management - Plan to undergo additional airway surgery at the time of AT. - Caregiver/child planning to move out of the area within 6 months. - Caregiver/child does not speak English or Spanish well enough to complete the behavioral and performance measures. - Child in foster care.

Study Design


Intervention

Procedure:
Adenotonsillectomy
Routine AT per clinical care.

Locations

Country Name City State
United States University of Michigan Health System Ann Arbor Michigan
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States University Hospitals-Case Medical Center Cleveland Ohio
United States University of Texas Southwestern Medical Center Dallas Texas
United States Children's Hospital of the King's Daughters Norfolk Virginia
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania

Sponsors (8)

Lead Sponsor Collaborator
Brigham and Women's Hospital Children's Hospital Medical Center, Cincinnati, Children's Hospital of Philadelphia, Children's Hospital of The King's Daughters, University Hospitals Cleveland Medical Center, University of Michigan, University of Rochester, University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (21)

Arozullah AM, Yarnold PR, Bennett CL, Soltysik RC, Wolf MS, Ferreira RM, Lee SY, Costello S, Shakir A, Denwood C, Bryant FB, Davis T. Development and validation of a short-form, rapid estimate of adult literacy in medicine. Med Care. 2007 Nov;45(11):1026-33. — View Citation

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Bull MJ; Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011 Aug;128(2):393-406. doi: 10.1542/peds.2011-1605. Epub 2011 Jul 25. Erratum in: Pediatrics. 2011 Dec;128(6):1212. — View Citation

Chervin RD, Hedger K, Dillon JE, Pituch KJ. Pediatric sleep questionnaire (PSQ): validity and reliability of scales for sleep-disordered breathing, snoring, sleepiness, and behavioral problems. Sleep Med. 2000 Feb 1;1(1):21-32. — View Citation

Clausen J, Sersen EA, Lidsky A. Sleep patterns in mental retardation: Down's syndrome. Electroencephalogr Clin Neurophysiol. 1977 Aug;43(2):183-91. — View Citation

de Miguel-Díez J, Villa-Asensi JR, Alvarez-Sala JL. Prevalence of sleep-disordered breathing in children with Down syndrome: polygraphic findings in 108 children. Sleep. 2003 Dec 15;26(8):1006-9. — View Citation

Diomedi M, Curatolo P, Scalise A, Placidi F, Caretto F, Gigli GL. Sleep abnormalities in mentally retarded autistic subjects: Down's syndrome with mental retardation and normal subjects. Brain Dev. 1999 Dec;21(8):548-53. — View Citation

Edgin JO, Tooley U, Demara B, Nyhuis C, Anand P, Spanò G. Sleep Disturbance and Expressive Language Development in Preschool-Age Children With Down Syndrome. Child Dev. 2015 Nov-Dec;86(6):1984-98. doi: 10.1111/cdev.12443. Epub 2015 Oct 5. — View Citation

Farhood Z, Isley JW, Ong AA, Nguyen SA, Camilon TJ, LaRosa AC, White DR. Adenotonsillectomy outcomes in patients with Down syndrome and obstructive sleep apnea. Laryngoscope. 2017 Jun;127(6):1465-1470. doi: 10.1002/lary.26398. Epub 2017 Jan 5. Review. — View Citation

Franco RA Jr, Rosenfeld RM, Rao M. First place--resident clinical science award 1999. Quality of life for children with obstructive sleep apnea. Otolaryngol Head Neck Surg. 2000 Jul;123(1 Pt 1):9-16. — View Citation

Garetz SL, Mitchell RB, Parker PD, Moore RH, Rosen CL, Giordani B, Muzumdar H, Paruthi S, Elden L, Willging P, Beebe DW, Marcus CL, Chervin RD, Redline S. Quality of life and obstructive sleep apnea symptoms after pediatric adenotonsillectomy. Pediatrics. 2015 Feb;135(2):e477-86. doi: 10.1542/peds.2014-0620. Epub 2015 Jan 19. — View Citation

Mai CT, Kucik JE, Isenburg J, Feldkamp ML, Marengo LK, Bugenske EM, Thorpe PG, Jackson JM, Correa A, Rickard R, Alverson CJ, Kirby RS; National Birth Defects Prevention Network. Selected birth defects data from population-based birth defects surveillance programs in the United States, 2006 to 2010: featuring trisomy conditions. Birth Defects Res A Clin Mol Teratol. 2013 Nov;97(11):709-25. doi: 10.1002/bdra.23198. — View Citation

Marcus CL, Keens TG, Bautista DB, von Pechmann WS, Ward SL. Obstructive sleep apnea in children with Down syndrome. Pediatrics. 1991 Jul;88(1):132-9. — View Citation

Nisbet LC, Phillips NN, Hoban TF, O'Brien LM. Characterization of a sleep architectural phenotype in children with Down syndrome. Sleep Breath. 2015 Sep;19(3):1065-71. doi: 10.1007/s11325-014-1094-6. Epub 2014 Dec 12. — View Citation

Owens JA, Spirito A, McGuinn M. The Children's Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged children. Sleep. 2000 Dec 15;23(8):1043-51. — View Citation

Presson AP, Partyka G, Jensen KM, Devine OJ, Rasmussen SA, McCabe LL, McCabe ER. Current estimate of Down Syndrome population prevalence in the United States. J Pediatr. 2013 Oct;163(4):1163-8. doi: 10.1016/j.jpeds.2013.06.013. Epub 2013 Jul 23. — View Citation

Rajagopal KR, Abbrecht PH, Derderian SS, Pickett C, Hofeldt F, Tellis CJ, Zwillich CW. Obstructive sleep apnea in hypothyroidism. Ann Intern Med. 1984 Oct;101(4):491-4. — View Citation

Reckley LK, Fernandez-Salvador C, Camacho M. The effect of tonsillectomy on obstructive sleep apnea: an overview of systematic reviews. Nat Sci Sleep. 2018 Apr 4;10:105-110. doi: 10.2147/NSS.S127816. eCollection 2018. Review. — View Citation

Redline S, Tishler PV, Schluchter M, Aylor J, Clark K, Graham G. Risk factors for sleep-disordered breathing in children. Associations with obesity, race, and respiratory problems. Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1527-32. — View Citation

Sherman SL, Allen EG, Bean LH, Freeman SB. Epidemiology of Down syndrome. Ment Retard Dev Disabil Res Rev. 2007;13(3):221-7. Review. — View Citation

Yang Q, Rasmussen SA, Friedman JM. Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study. Lancet. 2002 Mar 23;359(9311):1019-25. — View Citation

* Note: There are 21 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary % enrolled/approached Percentage of families approached for participation that sign informed consent to participate. 1 year
Primary % retained/enrolled Percentage of consented families that completed study participation. 1 year
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