Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder - Full Text View

Sponsored by:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00429273

Purpose

This study will evaluate the effectiveness of a single drug versus a combination of drugs in treating attention deficit hyperactivity disorder in children.

Condition	Intervention	Phase
Attention Deficit Disorder With Hyperactivity	Drug: Guanfacine Drug: Methylphenidate (MPH) Drug: Combined methylphenidate and guanfacine	Phase IV

MedlinePlus related topics: Attention Deficit Hyperactivity Disorder

Drug Information available for: Methylphenidate hydrochloride Methylphenidate Guanfacine Guanfacine hydrochloride Dexmethylphenidate Dexmethylphenidate hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	An Eight-Week, Randomized, Double-Blind Comparison of Guanfacine, Focalin XR, and the Combination, With a Twelve Month Open-Label Extension for the Treatment of ADHD in Pediatric Subjects Aged 7 to 14 Years

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Score on ADHD IV Rating Scale (ADHD-RS) [ Time Frame: Measured at baseline and Weeks 0 to 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Score on behavioral ratings CGI-Improvement, Conners Global Index and cognitive test measures [ Time Frame: Measured at baseline and Weeks 0 to 8 ] [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	January 2007
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Active Comparator Participants will take guanfacine only	Drug: Guanfacine Week 1: 0.5 mg twice daily; Week 2: 1 mg twice daily; Week 3: 1.5 mg twice daily; Weeks 4 through 8: best dose as determined by efficacy measures
Group 2: Active Comparator Participants will take methylphenidate only	Drug: Methylphenidate (MPH) Participants less than 25 kg will receive 10 mg once daily for Week 5, 20 mg once daily for Week 6, and 30 mg once daily for Week 7. Subjects greater than 25 kg will receive 20 mg once daily for Week 5, 30 mg once daily for Week 6, 40 mg once daily for Week 7, and best doses as determined by efficacy measures for Week 8.
Group 3: Experimental Participants will take guanfacine and methylphenidate combined	Drug: Combined methylphenidate and guanfacine Dosing as described for guanfacine and methylphenidate

Detailed Description:

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood mental disorders. Children with ADHD have impaired functioning in multiple settings, including home and school. They also have difficulty relating with peers. If left untreated, the disorder may cause adverse effects that can last into adolescence and adulthood. Stimulant medications, such as methylphenidate, are effective in reducing ADHD symptoms on a short-term basis. However, few long-term benefits in academic or general functioning from current ADHD therapies have been demonstrated. Focalin XR is a stimulant medication that is FDA-approved for treating ADHD. Guanfacine is another medication that is currently approved for the treatment of hypertension, but has long been used for treating ADHD. This study will determine the effectiveness of a combination of Focalin XR and guanfacine in enhancing cognitive functioning and improving the long-term benefit of ADHD treatment.

Participants in this study will be randomly assigned to one of three treatment regimens: Focalin XR and placebo; guanfacine and placebo; or Focalin XR and guanfacine. The study will be conducted in two phases: an 8-week double-blind treatment phase and a 12-month open-label treatment phase. In Phase I, one third of participants will receive placebo for the initial 4 weeks, followed by Focalin XR alone for the remaining 4 weeks. All other participants will receive their assigned medications for the full 8 weeks. All participants will attend two study visits prior to beginning treatment and one study visit per week throughout Phase I. At the end of Phase I, treatment assignments will be unblinded. Participants who experienced adequate improvement with their assigned treatment will then continue in Phase II on the same medication(s) for an additional 12 months. Participants will attend study visits once per month until the end of the study. Study visits will include self-report measures, clinical assessments, and cognitive testing. Participants will also undergo four electroencephalography (EEG) tests and two fMRI scans over the course of the study. All Phase II participants will receive a follow-up telephone call 1 month after the final study visit.

Eligibility

Ages Eligible for Study:	7 Years to 14 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of DSM-IV ADHD by K-SADS-PL and confirmed by clinical interview
Clinical Global Impression-Severity score of at least 4 for ADHD
Resided with primary caretaker for at least 6 months prior to study entry

Exclusion Criteria:

History of autism, pervasive developmental disorder, chronic tic disorder, psychosis, or bipolar disorder
Current major depression or panic disorder
Systolic or diastolic blood pressure at screening greater than the 95th percentile or less than the 5th percentile for age and body mass index (BMI)
Any medical condition that might make stimulant or alpha agonist therapy medically inadvisable
Need for chronic use of other medications with central nervous system effects
Pregnant, breastfeeding, or beyond menarche and has a positive urine pregnancy test
History of structural heart defects, syncope, or fainting while exercising
Clinically significant cardiac abnormality as determined by echocardiogram (ECG) at study entry
Mental retardation as determined by clinical functional assessment and an IQ estimate of less than 70 based on Wechsler Adult Intelligence Scale (WAIS) subtests

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429273

Contacts

Contact: Joni Zuckerbrow-Miller

310-295-7667

jzuckerbrow@mednet.ucla.edu

Locations

United States, California
University of California Los Angeles	Recruiting
Los Angeles, California, United States, 90095
Contact: Fiona Whelan, M.S. 310-825-7874 fwhelan@mednet.ucla.edu
Principal Investigator: James T. McCracken, MD
Sub-Investigator: James J. McGough, MD
Sub-Investigator: Robert Bilder, Ph.D.

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:	James T. McCracken, MD	University of California, Los Angeles
Study Director:	James J. McGough, MD	University of California, Los Angeles

More Information

Responsible Party:	UCLA ( James McCracken, MD )
Study ID Numbers:	P50 MH77248, DDTR B2-NDH
Study First Received:	January 29, 2007
Last Updated:	October 24, 2008
ClinicalTrials.gov Identifier:	NCT00429273
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

ADHD
Guanfacine
Methylphenidate
Focalin XR

Pediatric
Cognitive function
Combination therapy

Study placed in the following topic categories:

Signs and Symptoms
Dopamine
Attention Deficit Disorder with Hyperactivity
Guanfacine
Mental Disorders
Mental Disorders Diagnosed in Childhood

Methylphenidate
Neurologic Manifestations
Attention Deficit and Disruptive Behavior Disorders
Hyperkinesis
Dyskinesias

Additional relevant MeSH terms:

Dopamine Uptake Inhibitors
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Adrenergic alpha-Agonists
Disease
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Physiological Effects of Drugs

Central Nervous System Stimulants
Cardiovascular Agents
Antihypertensive Agents
Adrenergic Agonists
Pharmacologic Actions
Pathologic Processes
Therapeutic Uses
Dopamine Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 30, 2009