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Sleep and Tolerability Study: Comparing the Effects of Adderall XR and Focalin XR

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ClinicalTrials.gov Identifier: NCT00393042
Recruitment Status : Completed
First Posted : October 26, 2006
Results First Posted : April 19, 2017
Last Update Posted : April 19, 2017
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Mark Stein, University of Illinois at Chicago

Tracking Information
First Submitted Date  ICMJE October 25, 2006
First Posted Date  ICMJE October 26, 2006
Results First Submitted Date  ICMJE December 16, 2015
Results First Posted Date  ICMJE April 19, 2017
Last Update Posted Date April 19, 2017
Study Start Date  ICMJE January 2006
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 7, 2017)
  • Sleep Start Time, and End Time as Determined by Actigraph and Sleep Diary Over 8 Weeks. [ Time Frame: 8-10 weeks ]
    Actigraphs (AW64 series) were worn each night and were used to assess participant's sleep patterns in their natural home environment. These computerized wristwatch-like devices collect data generated by movements. They are minimally invasive and allow sleep to be recorded reliably without interfering with the family's routine. One-minute epochs were used to analyze actigraphic sleep sata. Bedtimes and wake times were reported for each participant using sleep logs, and these times were used as the start and end times for the analyses. For each 1-min epoch, the total sum of activity counts were computed. If they exceeded a threshold (threshold sensitivity value = mean score in active period/45), then the epoch was considered waking. If it fell below that threshold, then it was considered sleep. The data for Adderall XR and Focalin XR was combined to look at the cumulative effects that medication has on sleep.
  • Sleep Duration [ Time Frame: 8-10 weeks ]
    Actigraphs (AW64 series) were worn each night and were used to assess participant's sleep patterns in their natural home environment. These computerized wristwatch-like devices collect data generated by movements. They are minimally invasive and allow sleep to be recorded reliably without interfering with the family's routine. One-minute epochs were used to analyze actigraphic sleep sata. Bedtimes and wake times were reported for each participant using sleep logs, and these times were used as the start and end times for the analyses. For each 1-min epoch, the total sum of activity counts were computed. If they exceeded a threshold (threshold sensitivity value = mean score in active period/45), then the epoch was considered waking. If it fell below that threshold, then it was considered sleep.The data for Adderall XR and Focalin XR was combined to look at the cumulative effects that medication has on sleep.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2006)
Number of minutes to sleep onset as determined by actigraph and sleep diary over 8 weeks.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2017)
  • ADHD Parent Rating Scale-IV [ Time Frame: completed weekly over 8-10 weeks ]
    Measures the severity of Total ADHD symptoms, Inattention and Hyperactivity/Impulsive symptoms. The Inattention and Hyperactivity/Impulsive symptoms can range from 0 to 27 each, with a higher score reflecting more severe ADHD symptoms. The total score is calculated by summing the inattention and Hyperactivity/Impulsive subscales. The total score can range from 0 to 54 with a higher score reflecting more severe ADHD symptoms.
  • Dopamine Active Transporter (DAT) 1 Gene Type Effects on ADHD Symptoms [ Time Frame: 8-10 weeks ]
    Three variations of the DAT 1 gene were observed, the 9/9 allele, the 9/10 allele and the 10/10 allele. The ADHD Rating Scale (ADHD-RS) and Clinical Global Impressions - Severity (CGI-S) measures were used to evaluate how the DAT 1 gene allele type altered the efficacy of the medication. The DAT 1 genotype did not predict differential response to Focalin XR or Adderall XR so the dose levels of each drug was combined to examine how the genotype interacted with the dose level. The ADHD-RS evaluates the severity of the participant's ADHD symptoms and includes two subscales: Inattention and Hyperactivity/Impulsivity. Both subscale scores range from 0 to 27 with a higher score representing more severe symptoms. The subscales are summed to calculate the total score which can range from 0 to 54. The CGI-S scale summarizes the clinician's impression of the participant's symptom severity and ranges from 1-7 with 1 representing normal (not at all ill) and 7 representing extremely ill.
  • Clinical Global Impression - Severity [ Time Frame: 8-10 weeks ]
    The CGI-S scale summarizes the clinician's impression of the participant's symptom severity and ranges from 1-7 with 1 representing normal (not at all ill) and 7 representing extremely ill.
  • Weiss Functional Impairment Rating Scale (WFIRS) [ Time Frame: 8-10 weeks ]
    The WFIRS consists of 50 questions where respondents are asked to rate their child's functional impairment. The items of the WFIRS are scored on a four point Likert-type rating scale: 0 (never or not at all), 1 (sometimes or somewhat), 2 (often or much) or 3 (very often or very much) and aggregated to produce six domain scores: Family (ranges between 0-24), Learning or School (ranges between 0-33), Self-Concept (ranges between 0-15), Social Activities (ranges between 0-27), Life Skills (ranges between 0-36), and Risky Activities (ranges between 0-42). The subscales are scored by summing the responses in the subsection. The Total score is the sum of all the responses and it ranges between 0-150. The higher the score in each of the subscales the more impairment is recorded, this is also true for the total score.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2006)
  • Ratings of ADHD symptoms along with parent, self report and clinician ratings of mood, tolerability, stimulant side effects, functional outcomes (e.g. family conflicts), and vital signs over a period of 8 weeks.
  • The number of 10 repeat alleles of DAT1 as correlated with ADHD symptoms and CGI-S ratings.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sleep and Tolerability Study: Comparing the Effects of Adderall XR and Focalin XR
Official Title  ICMJE Sleep and Tolerability of Extended Release Dexmethylphenidate vs. Mixed Amphetamine Salts: A Double Blind, Placebo Controlled Study (SAT STUDY)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Attention Deficit Hyperactivity Disorder
Intervention  ICMJE
  • Drug: Dexmethylphenidate
    10, 20, 25-30 mg.
    Other Name: Focalin XR
  • Drug: Mixed Amphetamine Salts, ER
    10, 20, 25-30
    Other Name: Adderall XR
  • Drug: placebo
    randomized placebo week during each 4 week period
Study Arms  ICMJE
  • Experimental: Focalin XR then Adderall XR
    Subjects are given the Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week followed by Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week.
    Interventions:
    • Drug: Dexmethylphenidate
    • Drug: Mixed Amphetamine Salts, ER
    • Drug: placebo
  • Experimental: Adderall XR then Focalin XR
    Subjects are given the Adderall XR (mixed amphetamine salts) for four weeks with a randomized placebo week followed by Focalin XR first (dexmethylphenidate) for four weeks with a randomized placebo week.
    Interventions:
    • Drug: Dexmethylphenidate
    • Drug: Mixed Amphetamine Salts, ER
    • Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2010)
77
Original Enrollment  ICMJE
 (submitted: October 25, 2006)
70
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date February 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 9 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00393042
Other Study ID Numbers  ICMJE CRIT124E US15
2006-0423
2006-04
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mark Stein, University of Illinois at Chicago
Study Sponsor  ICMJE Seattle Children's Hospital
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: Mark A Stein, PhD University of Illinois-Chicago; Hyperactivity, Attention and Learning Problems Clinic (HALP)
Principal Investigator: Elizabeth Charney, MD University of Illinois-Chicago, Hyperactivity, Attention, and Learning Problems Clinic (HALP)
PRS Account Seattle Children's Hospital
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP