Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
Condition: ADHD; Attention Deficit Hyperactivity Disorder
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Guanfacine Hydrochloride XR; Placebo
Intervention description: Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose; Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
Intervention MeSH terms: Guanfacine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 8 Years
Maximum age: 15 Years
Healthy volunteers: No
Keywords: Intuniv; Attention Deficit Hyperactivity Disorder; fMRI

Summary:

      This study proposes to evaluate the effects of guanfacine extended release on brain
      activation during fMRI in children and adolescents with ADHD between the ages 8-15 and ADHD
      subjects randomized to placebo treatment.

      This study also proposes to collect DNA on study participants, to examine the genetic
      underpinning of the observed fMRI activation profiles at baseline and in response to
      treatment. The purpose is to examine polymorphisms of the adrenergic 2A gene (and other
      related targets) for genetic biomarkers in association with the fMRI findings of this study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of any subtype of ADHD

          -  Normal findings on physical exam, laboratory studies, vital signs, and ECG

          -  Weight = 60 kgs or less

          -  Able to complete study procedures and swallow capsules;

          -  Willing to commit to the entire visit schedule

          -  Off treatment or have been discontinued from their previous medication for two weeks.

        Exclusion Criteria:

          -  Psychiatric comorbidity except Oppositional Defiant Disorder [ODD], Simple Phobia, and
             dysthymia (unless ongoing medication treatment is required);

          -  Currently a suicide risk, has previously made a suicide attempt or has a prior history
             of suicidal behavior;

          -  Has failed treatment with an adequate trial of an alpha-2 adrenergic agonist;

          -  Known or suspected allergy, hypersensitivity, or clinically significant intolerance to
             guanfacine hydrochloride.

        Children may not:

          -  be treated with systemic medication for a medical or psychiatric illness that have CNS
             effects or affect cognitive function;

          -  have a known history or presence of structural cardiac abnormalities, exercise-related
             cardiac events, or clinically significant bradycardia;

          -  have orthostatic hypotension or a known history of hypertension;

          -  have an abnormal ECG that is deemed clinically significant;

          -  have a history of alcohol or other substance abuse or dependence within the last 6
             months;

          -  use any medications that affect BP or heart rate (excluding the subject's current ADHD
             medication at screening);

          -  use another investigational medicinal product or participation in a clinical study
             within 30 days prior to the baseline visit;

          -  be significantly overweight based on Center for Disease Control and Prevention Body
             Mass Index (BMI)-for-age gender specific charts;

          -  have body weight of less than 25kg;

          -  have a clinically important abnormality on urine drug and alcohol screen (excluding
             the subject's current ADHD stimulant, if applicable);

          -  be female and currently pregnant or lactating;

          -  have symptoms indicative of a primary sleep disorder.

          -  have braces or other metal permanently placed within their body.

          -  be too anxious to tolerate the fMRI procedure, or be claustrophobic.