Clinical trial NCT00429273: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Disorder With Hyperactivity
Keywords: ADHD
Guanfacine
Methylphenidate
Focalin XR
Pediatric
Cognitive function
Combination therapy
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2007-01-31
Enrollment: 212
Sex: ALL
Minimum age (years): 7
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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

Primary outcomes:
measure: ADHD IV Rating Scale (Attention Deficit Hyperactivity Disorder Rating Scale)
timeFrame: Measured at baseline Week 4 and Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: James T. McCracken, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: James J. McGough, MD
role: STUDY_DIRECTOR
References:
citation: Michelini G, Lenartowicz A, Vera JD, Bilder RM, McGough JJ, McCracken JT, Loo SK. Electrophysiological and Clinical Predictors of Methylphenidate, Guanfacine, and Combined Treatment Outcomes in Children With Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2023 Apr;62(4):415-426. doi: 10.1016/j.jaac.2022.08.001. Epub 2022 Aug 10.
citation: Michelini G, Lenartowicz A, Diaz-Fong JP, Bilder RM, McGough JJ, McCracken JT, Loo SK. Methylphenidate, Guanfacine, and Combined Treatment Effects on Electroencephalography Correlates of Spatial Working Memory in Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2023 Jan;62(1):37-47. doi: 10.1016/j.jaac.2022.06.017. Epub 2022 Aug 10.
citation: Sayer GR, McGough JJ, Levitt J, Cowen J, Sturm A, Castelo E, McCracken JT. Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2016 Dec;26(10):882-888. doi: 10.1089/cap.2015.0264. Epub 2016 Aug 2.
citation: Loo SK, Bilder RM, Cho AL, Sturm A, Cowen J, Walshaw P, Levitt J, Del'Homme M, Piacentini J, McGough JJ, McCracken JT. Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):674-682.e1. doi: 10.1016/j.jaac.2016.04.020. Epub 2016 May 21.
citation: Bilder RM, Loo SK, McGough JJ, Whelan F, Hellemann G, Sugar C, Del'Homme M, Sturm A, Cowen J, Hanada G, McCracken JT. Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):667-73. doi: 10.1016/j.jaac.2016.05.016. Epub 2016 Jun 7.
citation: McCracken JT, McGough JJ, Loo SK, Levitt J, Del'Homme M, Cowen J, Sturm A, Whelan F, Hellemann G, Sugar C, Bilder RM. Combined Stimulant and Guanfacine Administration in Attention-Deficit/Hyperactivity Disorder: A Controlled, Comparative Study. J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):657-666.e1. doi: 10.1016/j.jaac.2016.05.015. Epub 2016 Jun 3.