REST: Understanding Sleep Problems in Children With Autism Spectrum Disorder
Study Details
Study Description
Brief Summary
The investigators will examine whether sleep problems in children with autism spectrum disorder (ASD) are related to alterations in the production of melatonin (MT), a hormone that plays an important role in regulating sleep-wake cycle. Children with ASD experience high rates of sleep disturbances that potentially contribute to problems with thinking and behavior. It is unclear if changes in MT production cause sleep problems in children with ASD. MT is frequently used to treat these sleep problems; however, it has not been well established whether MT is an effective treatment. Our hypotheses concerning MT is children with ASD and sleep problems will have a delayed sleep-wake cycle and/or decreased MT production. This study will compare children diagnosed with ASD to "healthy" control children with no ASD diagnosis. All subjects will be recruited from one of three sites: Baylor College of Medicine, Oregon Health & Science University and Columbia University. The investigators will use a standardized questionnaire to determine whether the child has sleep problems. The investigators will measure MT levels in saliva in ASD children with sleep problems and in a group of control children without sleep problems. Total 24-hour MT production will be determined from urine samples in these same two groups.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Detailed Description
This is a proposal to study the relationship between melatonin (MT) and sleep problems in children with autism spectrum disorder (ASD), as part of the collaborative research structure of the Autism Treatment Network (ATN). A major goal of the ATN is to conduct clinical research that will have a significant impact on the daily lives and functioning of individuals with ASD and to address immediate concerns of parents. Children with ASD experience high rates of sleep disturbance, which likely contribute to the severity of their daytime cognitive and behavioral dysfunction and to poorer quality of life for them and their families.
As a step toward addressing sleep problems in ASD, we propose to test the hypothesis that children with ASD and sleep problems will have a delay in MT onset and/or have decreased MT secretion over 24 hours compared to normal controls.
Primary endpoint: Characterize the endogenous MT profiles in children with ASD:
We predict that results from this study will reveal lower levels of metabolized MT in children with ASD when compared to normal children. In addition, we anticipate that children with ASD will have delayed MT onset or altered circadian phase.
Data from this study will provide important information concerning circadian rhythm dysregulation in ASD and will support the development of future studies using MT to modify and correct abnormal circadian rhythms.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
ASD children ASD children as defined by: Age greater than or equal to 4 or less than or equal to 9 years Diagnosis of Autism Spectrum Disorder; supported by ADOS and the ADI or SCQ (subjects). No current use of psychoactive medications (e.g. fluoxetine, methylphenidate, risperidone, lithium, etc.) No current or use within the last 1 month of beta-blockers or melatonin No current use of sleep aids No presence of untreated medical problems that could otherwise explain sleep problems (e.g. obstructive sleep apnea, gastroesophageal reflux disease - GERD) (6) No blindness. |
|
"Healthy" control children "Healthy" control children as defined by: Age greater than or equal to 4 or less than or equal to 9 years A SCQ score of less than 10 without parental or physician concern for another neurodevelopmental disorder will be used to define normal children. No current use of psychoactive medications (e.g. fluoxetine, methylphenidate, risperidone, lithium, etc.) No current or use within the last 1 month of beta-blockers or melatonin No current use of sleep aids; No presence of untreated medical problems that could otherwise explain sleep problems (e.g. obstructive sleep apnea, gastroesophageal reflux disease - GERD) (6) No blindness. (7) No current or past diagnosis of ADHD, depression, anxiety or with any other psychiatric conditions. (8) No sibling with a diagnosis of Autism Spectrum Disorder. |
Outcome Measures
Primary Outcome Measures
- Sleep Latency, as measured by actigraphy [1 week]
Secondary Outcome Measures
- Total sleep time, as measured by actigraphy [1 week]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of Autism Spectrum Disorder; supported by ADOS and the ADI or SCQ (subjects).
-
Age greater than or equal to 4 or less than or equal to 9 years;
-
Parents have given informed consent.
-
Parent/Caregiver fluent in written and spoken English.
-
Controls only: A SCQ score of less than 10 without parental or physician concern for another neurodevelopmental disorder will be used to define normal children.
Exclusion Criteria:
-
Current use of psychoactive medications (e.g. fluoxetine, methylphenidate, risperidone, lithium, etc.)*;
-
Current or use within the last 1 month of beta-blockers or melatonin;
-
Current use of sleep aids;
-
Presence of untreated medical problems that could otherwise explain sleep problems (e.g. obstructive sleep apnea, gastroesophageal reflux disease - GERD);
-
Blindness.
-
Controls only: current or past diagnosis of ADHD, depression, anxiety or with any other psychiatric conditions. (7) Controls only: Sibling has a diagnosis of Autism Spectrum Disorder.
- Psychoactive medications can be discontinued but the parents must discuss medication discontinuation with their prescribing physician prior to reducing or stopping the medications.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Columbia University | New York | New York | United States | 10032 |
2 | Oregon Health & Sciences University | Portland | Oregon | United States | 97239 |
3 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor College of Medicine
- Autism Speaks
- Oregon Health and Science University
- Columbia University
- The Emmes Company, LLC
- Autism Treatment Network
Investigators
- Study Director: Daniel G Glaze, M.D., Baylor College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
- Allik H, Larsson JO, Smedje H. Insomnia in school-age children with Asperger syndrome or high-functioning autism. BMC Psychiatry. 2006 Apr 28;6:18.
- Aman MG, Singh NN, Stewart AW, Field CJ. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects. Am J Ment Defic. 1985 Mar;89(5):485-91.
- Amminger GP, Berger GE, Schäfer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry. 2007 Feb 15;61(4):551-3. Epub 2006 Aug 22.
- Beebe DW, Wells CT, Jeffries J, Chini B, Kalra M, Amin R. Neuropsychological effects of pediatric obstructive sleep apnea. J Int Neuropsychol Soc. 2004 Nov;10(7):962-75.
- Bloom BJ, Owens JA, McGuinn M, Nobile C, Schaeffer L, Alario AJ. Sleep and its relationship to pain, dysfunction, and disease activity in juvenile rheumatoid arthritis. J Rheumatol. 2002 Jan;29(1):169-73.
- Bradley EA, Summers JA, Wood HL, Bryson SE. Comparing rates of psychiatric and behavior disorders in adolescents and young adults with severe intellectual disability with and without autism. J Autism Dev Disord. 2004 Apr;34(2):151-61.
- Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Baker G, Klassen TP, Vohra S. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med. 2005 Dec;20(12):1151-8.
- Chervin RD, Ruzicka DL, Giordani BJ, Weatherly RA, Dillon JE, Hodges EK, Marcus CL, Guire KE. Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics. 2006 Apr;117(4):e769-78.
- Clements J, Wing L, Dunn G. Sleep problems in handicapped children: a preliminary study. J Child Psychol Psychiatry. 1986 May;27(3):399-407.
- Couturier JL, Speechley KN, Steele M, Norman R, Stringer B, Nicolson R. Parental perception of sleep problems in children of normal intelligence with pervasive developmental disorders: prevalence, severity, and pattern. J Am Acad Child Adolesc Psychiatry. 2005 Aug;44(8):815-22.
- Dahl RE. The impact of inadequate sleep on children's daytime cognitive function. Semin Pediatr Neurol. 1996 Mar;3(1):44-50. Review.
- Didden R, Korzilius H, van Aperlo B, van Overloop C, de Vries M. Sleep problems and daytime problem behaviours in children with intellectual disability. J Intellect Disabil Res. 2002 Oct;46(Pt 7):537-47.
- Fallone G, Acebo C, Arnedt JT, Seifer R, Carskadon MA. Effects of acute sleep restriction on behavior, sustained attention, and response inhibition in children. Percept Mot Skills. 2001 Aug;93(1):213-29.
- Friedman BC, Hendeles-Amitai A, Kozminsky E, Leiberman A, Friger M, Tarasiuk A, Tal A. Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome. Sleep. 2003 Dec 15;26(8):999-1005.
- Garstang J, Wallis M. Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006 Sep;32(5):585-9.
- Giannotti F, Cortesi F, Cerquiglini A, Bernabei P. An open-label study of controlled-release melatonin in treatment of sleep disorders in children with autism. J Autism Dev Disord. 2006 Aug;36(6):741-52.
- Honomichl RD, Goodlin-Jones BL, Burnham M, Gaylor E, Anders TF. Sleep patterns of children with pervasive developmental disorders. J Autism Dev Disord. 2002 Dec;32(6):553-61.
- Hoshino Y, Watanabe H, Yashima Y, Kaneko M, Kumashiro H. An investigation on sleep disturbance of autistic children. Folia Psychiatr Neurol Jpn. 1984;38(1):45-51.
- Kendall AR, Lewy AJ, Sack RL. Effects of aging on the intrinsic circadian period of totally blind humans. J Biol Rhythms. 2001 Feb;16(1):87-95.
- Kennedy JD, Blunden S, Hirte C, Parsons DW, Martin AJ, Crowe E, Williams D, Pamula Y, Lushington K. Reduced neurocognition in children who snore. Pediatr Pulmonol. 2004 Apr;37(4):330-7.
- Kulman G, Lissoni P, Rovelli F, Roselli MG, Brivio F, Sequeri P. Evidence of pineal endocrine hypofunction in autistic children. Neuro Endocrinol Lett. 2000;21(1):31-34.
- Leibenluft E, Feldman-Naim S, Turner EH, Schwartz PJ, Wehr TA. Salivary and plasma measures of dim light melatonin onset (DLMO) in patients with rapid cycling bipolar disorder. Biol Psychiatry. 1996 Oct 15;40(8):731-5.
- Lewy AJ, Bauer VK, Hasler BP, Kendall AR, Pires ML, Sack RL. Capturing the circadian rhythms of free-running blind people with 0.5 mg melatonin. Brain Res. 2001 Nov 9;918(1-2):96-100.
- Lewy AJ, Cutler NL, Sack RL. The endogenous melatonin profile as a marker for circadian phase position. J Biol Rhythms. 1999 Jun;14(3):227-36.
- Lewy AJ, Emens J, Sack RL, Hasler BP, Bernert RA. Zeitgeber hierarchy in humans: resetting the circadian phase positions of blind people using melatonin. Chronobiol Int. 2003 Sep;20(5):837-52.
- Lewy AJ, Emens JS, Sack RL, Hasler BP, Bernert RA. Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period. Chronobiol Int. 2002 May;19(3):649-58.
- McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002 Aug 1;347(5):314-21.
- Mindell JA, Emslie G, Blumer J, Genel M, Glaze D, Ivanenko A, Johnson K, Rosen C, Steinberg F, Roth T, Banas B. Pharmacologic management of insomnia in children and adolescents: consensus statement. Pediatrics. 2006 Jun;117(6):e1223-32.
- Nir I, Meir D, Zilber N, Knobler H, Hadjez J, Lerner Y. Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. J Autism Dev Disord. 1995 Dec;25(6):641-54.
- O'Brien LM, Gozal D. Neurocognitive dysfunction and sleep in children: from human to rodent. Pediatr Clin North Am. 2004 Feb;51(1):187-202. Review.
- Owens JA, Spirito A, McGuinn M, Nobile C. Sleep habits and sleep disturbance in elementary school-aged children. J Dev Behav Pediatr. 2000 Feb;21(1):27-36.
- 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.
- Paavonen EJ, Nieminen-von Wendt T, Vanhala R, Aronen ET, von Wendt L. Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol. 2003 Spring;13(1):83-95.
- Pappu AS, Steiner RD, Connor SL, Flavell DP, Lin DS, Hatcher L, Illingworth DR, Connor WE. Feedback inhibition of the cholesterol biosynthetic pathway in patients with Smith-Lemli-Opitz syndrome as demonstrated by urinary mevalonate excretion. J Lipid Res. 2002 Oct;43(10):1661-9.
- Patzold LM, Richdale AL, Tonge BJ. An investigation into sleep characteristics of children with autism and Asperger's Disorder. J Paediatr Child Health. 1998 Dec;34(6):528-33.
- Polimeni MA, Richdale AL, Francis AJ. A survey of sleep problems in autism, Asperger's disorder and typically developing children. J Intellect Disabil Res. 2005 Apr;49(Pt 4):260-8.
- Posey DJ, Wiegand RE, Wilkerson J, Maynard M, Stigler KA, McDougle CJ. Open-label atomoxetine for attention-deficit/ hyperactivity disorder symptoms associated with high-functioning pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):599-610.
- Potocki L, Glaze D, Tan DX, Park SS, Kashork CD, Shaffer LG, Reiter RJ, Lupski JR. Circadian rhythm abnormalities of melatonin in Smith-Magenis syndrome. J Med Genet. 2000 Jun;37(6):428-33.
- Quine L. Sleep problems in children with mental handicap. J Ment Defic Res. 1991 Aug;35 ( Pt 4):269-90.
- Richdale AL, Prior MR. The sleep/wake rhythm in children with autism. Eur Child Adolesc Psychiatry. 1995 Jul;4(3):175-86.
- Robinson AM, Richdale AL. Sleep problems in children with an intellectual disability: parental perceptions of sleep problems, and views of treatment effectiveness. Child Care Health Dev. 2004 Mar;30(2):139-50.
- Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000 Oct 12;343(15):1070-7.
- Scahill L, Aman MG, McDougle CJ, McCracken JT, Tierney E, Dziura J, Arnold LE, Posey D, Young C, Shah B, Ghuman J, Ritz L, Vitiello B. A prospective open trial of guanfacine in children with pervasive developmental disorders. J Child Adolesc Psychopharmacol. 2006 Oct;16(5):589-98.
- Schreck KA, Mulick JA. Parental report of sleep problems in children with autism. J Autism Dev Disord. 2000 Apr;30(2):127-35.
- Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics. 2004 Nov;114(5):e634-41. Epub 2004 Oct 18.
- Tordjman S, Anderson GM, Pichard N, Charbuy H, Touitou Y. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol Psychiatry. 2005 Jan 15;57(2):134-8.
- Voultsios A, Kennaway DJ, Dawson D. Salivary melatonin as a circadian phase marker: validation and comparison to plasma melatonin. J Biol Rhythms. 1997 Oct;12(5):457-66.
- Weiss MD, Wasdell MB, Bomben MM, Rea KJ, Freeman RD. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):512-519. doi: 10.1097/01 chi.0000205706.78818.ef.
- Wiggs L, Stores G. Severe sleep disturbance and daytime challenging behaviour in children with severe learning disabilities. J Intellect Disabil Res. 1996 Dec;40 ( Pt 6):518-28.
- Wiggs L, Stores G. Sleep patterns and sleep disorders in children with autistic spectrum disorders: insights using parent report and actigraphy. Dev Med Child Neurol. 2004 Jun;46(6):372-80.
- 2003