Clinical trial NCT01709695: Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD
Official title: Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With Attention-deficit/Hyperactivity Disorder (ADHD): an Functional Magnetic Resonance Imaging(fMRI) Study of Brain Activation Pre and Post Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: ADHD
Attention Deficit Hyperactivity Disorder
Keywords: Intuniv
Attention Deficit Hyperactivity Disorder
fMRI
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2012-10-18
Enrollment: 27
Sex: ALL
Minimum age (years): 8
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This study proposes to evaluate the effects of guanfacine on brain activation during fMRI in 12 children and adolescents ages 8 - 15 with ADHD treated with once-daily INTUNIV(TM) (guanfacine; GXR) extended release tablets and 12 ADHD subjects randomized to placebo treatment. Children will be comprehensively assessed using a variety of clinical and neuropsychological measures. They will be scanned at baseline while performing both the go/no-go task (a well validated task for measuring inhibitory control (Durston et al., 2002, 2003)) and the Stay Alert task - a new task designed to measure the arousal component of attention, which was used successfully in a recent fMRI study of guanfacine in healthy adults (Clerkin et al., 2009). They will then be treated with GXR or placebo for 6 - 8 weeks in accordance with titration and dosing strategies used in recent Phase III dose optimization trials (e.g., up to 4 mg/day), and re-scanned while performing the same two tasks. The fMRI scans will be conducted using a dedicated research 3.0 T Siemens scanner.

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.

Primary outcomes:
measure: Go/No-go Task Performance Correct Inhibitions
timeFrame: Baseline and 8 weeks
measure: Go/No-go Task Reaction Time
timeFrame: Baseline and 8 weeks
measure: Go/No-go Task Performance Correct Responses
timeFrame: Baseline and 8 weeks
Secondary outcomes:
measure: Clinical Global Impressions (CGI-I)
timeFrame: up to 8 weeks
measure: Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)
timeFrame: up to 8 weeks
measure: Finger Windows
timeFrame: Baseline
measure: Digit Span
timeFrame: Baseline
measure: Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)
timeFrame: baseline and 8 weeks
measure: Continuous Performance Test - Commissions
timeFrame: Baseline
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Newcorn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bedard AC, Schulz KP, Krone B, Pedraza J, Duhoux S, Halperin JM, Newcorn JH. Neural mechanisms underlying the therapeutic actions of guanfacine treatment in youth with ADHD: a pilot fMRI study. Psychiatry Res. 2015 Mar 30;231(3):353-6. doi: 10.1016/j.pscychresns.2015.01.012. Epub 2015 Jan 19.