Neurobiological Basis of Response to Guanfacine Extended Release in Children and Adolescents With ADHD

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
Jeffrey Newcorn, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01709695
First received: August 30, 2012
Last updated: August 22, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
ADHD
Attention Deficit Hyperactivity Disorder
Drug: Guanfacine Hydrochloride XR
Drug: Placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Change in fMRI activation from pre to post treatment [ Time Frame: At screening and at 6-8 weeks. ] [ Designated as safety issue: No ]
    Change in fMRI activation from pre to post treatment in medication treated subjects in comparison to placebo treated subjects who are scanned while performing a go/no-go task.


Secondary Outcome Measures:
  • Clinical Global Impressions [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    Physician rated scales of overall clinical impairment (CGI-O), severity of clinical impairment (CGI-S), and clinical improvement (CGI-I)

  • Atomoxetine Stimulant Side Effects Rating Scale (ASSERS) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: Yes ]
    Side effects rating scale

  • Neuropsychological assessments [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    Neuropsychological assessments: Digit Span, Finger Windows, Continuous Performance Test, Attentional Network Task (ANT), and fMRI behavioral task data

  • Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV) [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    Norm referenced parent interview to assess severity and frequency of ADHD symptoms


Estimated Enrollment: 24
Study Start Date: March 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: guanfacine hydrochloride XR
Flexible dose titration of guanfacine extended release (Intuniv; active medication). The medication is titrated in doses from 1 - 4 mg once daily
Drug: Guanfacine Hydrochloride XR
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose
Other Names:
  • INTUNIV non-stimulant medication
  • GXR
Placebo Comparator: Placebo Group
Flexible dose titration of placebo
Drug: Placebo
Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

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

Ages Eligible for Study:   8 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT01709695

Contacts
Contact: Beth Krone, MS 212-241-8012 beth.krone@mssm.edu

Locations
United States, New York
Mount Sinai School of Medicine Recruiting
New York, New York, United States, 10029
Contact: Beth Krone, MS    212-241-8012    beth.krone@mssm.edu   
Principal Investigator: Jeffrey Newcorn, MD         
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Jeffrey Newcorn, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Jeffrey Newcorn, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01709695     History of Changes
Other Study ID Numbers: GCO 09-1825, HSM:10-00415
Study First Received: August 30, 2012
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Intuniv
Attention Deficit Hyperactivity Disorder
fMRI

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Disease
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Dyskinesias
Mental Disorders
Mental Disorders Diagnosed in Childhood
Nervous System Diseases
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Guanfacine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Antihypertensive Agents
Cardiovascular Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014