Clinical trial NCT00393042: Sleep and Tolerability Study: Comparing the Effects of Adderall XR and Focalin XR
Official title: Sleep and Tolerability of Extended Release Dexmethylphenidate vs. Mixed Amphetamine Salts: A Double Blind, Placebo Controlled Study (SAT STUDY)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: Attention Deficit Hyperactivity Disorder
sleep
side effects
stimulants
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2006-10-26
Enrollment: 77
Sex: ALL
Minimum age (years): 9
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate how children and adolescents with Attention Deficit/ Hyperactivity Disorder (ADHD) respond to treatment with three differing doses of stimulant medications used to treat ADHD, Adderall XR® and Focalin XR®. Another purpose of the study is to evaluate if there are differences in sleep and other side effects, such as changes in mood or loss of appetite, which can occur with stimulant medications. A third purpose is to determine if there are differences in the characteristics of individuals who respond better to either of the medications.

This research is being done because the investigators do not know if one of these two commonly used treatments is better tolerated than the other. Children and adolescents with ADHD often have a hard time sitting still, playing quietly, finishing things they start, paying attention, waiting their turn, and not distracting others. These medications improve these symptoms, but sometimes affect sleep, appetite, or mood.

It is hypothesized that at effective and frequently prescribed doses, Adderall will be associated with insomnia, more stimulant side effects, and decreased tolerability during an acute trial relative to Focalin.

Detailed description: ADHD is often treated with stimulant medications, which have demonstrated short-term efficacy in numerous trials. However, treatment is often discontinued prematurely. Although ADHD often persists through adolescence, approximately half of all children who are treated with a stimulant medication discontinue treatment within one year (Charach, Ickowicz et al. 2004). Presumably, tolerability and treatment compliance are highly related to the side effect profile of stimulant medications (Schachar, Jadad et al. 2002). Sleep problems, particularly insomnia, are frequently associated with ADHD and are often exacerbated by stimulant medications, particularly at higher doses. Other frequent stimulant side effects are decreased appetite and mood lability (dysphoria/euphoria). Little is known about the relative effects of different stimulant formulations and dosages (i.e amphetamine, methylphenidate, dexmethylphenidate) on sleep and tolerability. There is some preliminary data with short acting stimulants suggesting a higher prevalence of sleep and appetite problems with amphetamine relative to mph (Pelham, Aronoff et al. 1999). Several studies indicate that sleep and other stimulant side effects are dose related (Stein, Sarampote et al. 2003), although this has not been found in all studies. Moreover, it is unclear if there are differences between long-acting amphetamine and methylphenidate based stimulants in their side effect profile and tolerability. Thus, we will directly compare these two long acting stimulant medications on their side effect profile and tolerability, including measures of sleep, mood, and evening behavior (e.g., family conflicts). The recently developed extended release formulation of dexmethylphenidate will be compared to one of the most common treatments for ADHD, extended release formulation of mixed amphetamine salts. The subject population will be older children and adolescents (10-17) with ADHD who are most likely to be treated with moderate to higher dose levels of stimulant medications and can complete all self-report measures.

Eligibility criteria: Inclusion Criteria:

* Any ADHD subtype, determined by KSADS interview (Kaufman, Birmaher et al. 1997). Comorbidity will likewise be allowed, to ensure representation.
* Signed informed consent and assent
* Clinical Global Impressions - Severity for ADHD (CGI-S-ADHD) rating is greater than or equal to 4
* Findings on physical exam, laboratory studies, vital signs, and ECG are judged to be normal for age
* Pulse and blood pressure are within 95% of age and gender mean
* Able to complete study instruments and swallow capsules
* Willing to commit to the entire visit schedule for the study, including at least one visit to UIC Medical Center.

Exclusion Criteria:

* Previous diagnosis of mental retardation
* Non-responder to either medication at the doses offered in the study in an adequate trial
* Must not have experienced disabling adverse effects with either medication
* Concomitant psychotropic medications are required or medications which might have a CNS effect
* Any other medical condition which represents a contraindication for either treatment is present
* History of alcohol or drug abuse in the past 3 months, or a positive urinary toxic screen on initial evaluation that is not explained by a time-limited medical circumstance
* Females of childbearing age who are sexually active, do not use acceptable birth control (double protection method), and after counseling, are unwilling to do so
* History of allergic reactions to multiple medications
* A history of psychosis
* Diagnosis of bipolar disorder

Primary outcomes:
measure: Sleep Start Time, and End Time as Determined by Actigraph and Sleep Diary Over 8 Weeks.
timeFrame: 8-10 weeks
measure: Sleep Duration
timeFrame: 8-10 weeks
Secondary outcomes:
measure: ADHD Parent Rating Scale-IV
timeFrame: completed weekly over 8-10 weeks
measure: Dopamine Active Transporter (DAT) 1 Gene Type Effects on ADHD Symptoms
timeFrame: 8-10 weeks
measure: Clinical Global Impression - Severity
timeFrame: 8-10 weeks
measure: Weiss Functional Impairment Rating Scale (WFIRS)
timeFrame: 8-10 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Northbrook
country: United States
facility: Northbrook HALP Clinic/ADHD Research Center
state: Illinois
Study officials:
affiliation: University of Illinois-Chicago; Hyperactivity, Attention and Learning Problems Clinic (HALP)
name: Mark A Stein, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Illinois-Chicago, Hyperactivity, Attention, and Learning Problems Clinic (HALP)
name: Elizabeth Charney, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997 Jul;36(7):980-8. doi: 10.1097/00004583-199707000-00021.
citation: Charach A, Figueroa M, Chen S, Ickowicz A, Schachar R. Stimulant treatment over 5 years: effects on growth. J Am Acad Child Adolesc Psychiatry. 2006 Apr;45(4):415-21. doi: 10.1097/01.chi.0000199026.91699.20.
citation: Schachar R, Jadad AR, Gauld M, Boyle M, Booker L, Snider A, Kim M, Cunningham C. Attention-deficit hyperactivity disorder: critical appraisal of extended treatment studies. Can J Psychiatry. 2002 May;47(4):337-48. doi: 10.1177/070674370204700404.
citation: Pelham WE, Aronoff HR, Midlam JK, Shapiro CJ, Gnagy EM, Chronis AM, Onyango AN, Forehand G, Nguyen A, Waxmonsky J. A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder. Pediatrics. 1999 Apr;103(4):e43. doi: 10.1542/peds.103.4.e43.
citation: Stein MA, Sarampote CS, Waldman ID, Robb AS, Conlon C, Pearl PL, Black DO, Seymour KE, Newcorn JH. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics. 2003 Nov;112(5):e404. doi: 10.1542/peds.112.5.e404.
citation: Stein MA, Waldman ID, Charney E, Aryal S, Sable C, Gruber R, Newcorn JH. Dose effects and comparative effectiveness of extended release dexmethylphenidate and mixed amphetamine salts. J Child Adolesc Psychopharmacol. 2011 Dec;21(6):581-8. doi: 10.1089/cap.2011.0018. Epub 2011 Dec 2.
citation: Santisteban JA, Stein MA, Bergmame L, Gruber R. Effect of extended-release dexmethylphenidate and mixed amphetamine salts on sleep: a double-blind, randomized, crossover study in youth with attention-deficit hyperactivity disorder. CNS Drugs. 2014 Sep;28(9):825-33. doi: 10.1007/s40263-014-0181-3.