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

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

Sleep and Tolerability of Extended Release Dexmethylphenidate vs. Mixed Amphetamine Salts: A Double Blind, Placebo Controlled Study (SAT STUDY)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393042
• Other study ID #: CRIT124E US15
• Secondary ID: 2006-04232006-04
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2006
• Last updated: September 27, 2010
• Start date: January 2006
• Est. completion date: February 2009

Study information

• Verified date: September 2010
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 9 Years to 17 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Dexmethylphenidate XR
10, 20, 25-30 mg.
• Mixed Amphetamine Salts, ER
10, 20, 25-30
• placebo
randomized placebo during each period

Locations

Country	Name	City	State
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Northbrook HALP Clinic/ADHD Research Center	Northbrook	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
University of Illinois at Chicago	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of minutes to sleep onset as determined by actigraph and sleep diary over 8 weeks.Ratings of side effects, mood.		8-10 weeks	Yes
Secondary	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.		8-10 weeks	Yes
Secondary	The number of 10 repeat alleles of DAT1 as correlated with ADHD symptoms and CGI-S ratings.		First week	No
Secondary	Family Conflicts		8-10 weeks	No
Secondary	ADHD Symptoms		8-10 weeks	No