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

NCT00393042 | Completed Phase 3 Results DMC

• 3 other identifiers: CRIT124E US152006-04232006-04
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 2

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.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Attention Deficit Hyperactivity Disorder; sleep; side effects; stimulants

Outcome Measures

Primary Outcomes (2)

• Sleep Start Time, and End Time as Determined by Actigraph and Sleep Diary Over 8 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.

  8-10 weeks

• Sleep Duration

  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.

  8-10 weeks

Secondary Outcomes (4)

• ADHD Parent Rating Scale-IV

  completed weekly over 8-10 weeks

• Dopamine Active Transporter (DAT) 1 Gene Type Effects on ADHD Symptoms

  8-10 weeks

• Clinical Global Impression - Severity

  8-10 weeks

• Weiss Functional Impairment Rating Scale (WFIRS)

  8-10 weeks

Study Arms (2)

Focalin XR then Adderall XR

EXPERIMENTAL

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.

Drug: Dexmethylphenidate; Drug: Mixed Amphetamine Salts, ER; Drug: placebo

Adderall XR then Focalin XR

EXPERIMENTAL

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.

Drug: Dexmethylphenidate; Drug: Mixed Amphetamine Salts, ER; Drug: placebo

Interventions

Dexmethylphenidate DRUG

10, 20, 25-30 mg.

Also known as: Focalin XR

Adderall XR then Focalin XR; Focalin XR then Adderall XR

Mixed Amphetamine Salts, ER DRUG

10, 20, 25-30

Also known as: Adderall XR

Adderall XR then Focalin XR; Focalin XR then Adderall XR

placebo DRUG

randomized placebo week during each 4 week period

Adderall XR then Focalin XR; Focalin XR then Adderall XR

Eligibility Criteria

• Age: 9 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Novartis: collaborator

Study Sites (2)

University of Illinois at Chicago

Chicago, Illinois, 60608, United States

Location

Northbrook HALP Clinic/ADHD Research Center

Northbrook, Illinois, 60062, United States

Location

Related Publications (7)

• 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.

  PMID: 9204677 BACKGROUND

• 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.

  PMID: 16601646 BACKGROUND

• 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.

  PMID: 12025432 BACKGROUND

• 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.

  PMID: 10103335 BACKGROUND

• 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.

  PMID: 14595084 BACKGROUND

• 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.

  PMID: 22136094 RESULT

• 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.

  PMID: 25056567 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Dexmethylphenidate Hydrochloride; SLI381

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Methylphenidate; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Due to early withdrawal or loss of contact during the study, the sample size for analysis was smaller. The dosing design of the study may have led to more adverse events than would occur in clinic.

Results Point of Contact

• Title: Dr. Mark Stein
• Organization: Dept. of Psychiatry, University of Washington

mstein42@uw.edu

206-987-1161

Study Officials

• 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)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 25, 2006
• First Posted: October 26, 2006
• Study Start: January 1, 2006
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: April 19, 2017
• Results First Posted: April 19, 2017

Record last verified: 2017-03

Locations

US (2)