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Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1)

This study has been completed.
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
James McCracken, University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00429273
First received: January 29, 2007
Last updated: January 11, 2016
Last verified: January 2016
  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)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

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 ]

Enrollment: 180
Study Start Date: January 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
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
Other Name: Tenex
Active Comparator: Group 2
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.
Other Name: Focalin XR
Experimental: Group 3
Participants will take guanfacine and methylphenidate combined
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
Other Name: Tenex
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.
Other Name: Focalin XR

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: Methylphenidate (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   (Child)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
University of California Los Angeles
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Los Angeles
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: James McCracken, Chair, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00429273     History of Changes
Other Study ID Numbers: P50MH077248-01  DDTR B2-NDH  10-000453 
Study First Received: January 29, 2007
Last Updated: January 11, 2016
Health Authority: United States: Federal Government

Keywords provided by University of California, Los Angeles:
ADHD
Guanfacine
Methylphenidate
Focalin XR
Pediatric
Cognitive function
Combination therapy

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Methylphenidate
Dexmethylphenidate Hydrochloride
Guanfacine
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Antihypertensive Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents

ClinicalTrials.gov processed this record on September 30, 2016