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”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: July 2011

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.

Intervention(s) in this Clinical Trial

• Drug: Methylphenidate (MPH)
  • 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
• Drug: Guanfacine
  • 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.
• Drug: Combined methylphenidate and guanfacine
  • Dosing as described for guanfacine and methylphenidate

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Group 1
  • Participants will take guanfacine only
• Active Comparator: Group 2
  • Participants will take methylphenidate only
• Experimental: Group 3
  • Participants will take guanfacine and methylphenidate combined

Primary Measures

• Score on ADHD IV Rating Scale (ADHD-RS)
  • Time Frame: Measured at baseline and Weeks 0 to 8
    Safety Issue?: No

Secondary Measures

• Score on behavioral ratings CGI-Improvement, Conners Global Index and cognitive test measures
  • Time Frame: Measured at baseline and Weeks 0 to 8
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of DSM-IV ADHD Combined Type 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 7 Years

Maximum Age for this Clinical Trial: 14 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

James T. McCracken, MD Principal Investigator University of California, Los Angeles  

Overall Contact: Joni Zuckerbrow-Miller 310-295-7667 jzuckerbrow@mednet.ucla.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00429273

Study ID Number: P50 MH77248

ClinicalTrials.gov Identifier: NCT00429273

Health Authority: United States: Federal Government