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

NCT01709695 | Completed Phase 4 Results DMC

• 2 other identifiers: GCO 09-1825HSM:10-00415
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

ADHD; Attention Deficit Hyperactivity Disorder

Keywords

Intuniv; Attention Deficit Hyperactivity Disorder; fMRI

Outcome Measures

Primary Outcomes (3)

• Go/No-go Task Performance Correct Inhibitions

  Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.

  Baseline and 8 weeks

• Go/No-go Task Reaction Time

  Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.

  Baseline and 8 weeks

• Go/No-go Task Performance Correct Responses

  Measures of go/no-go task performance during functional magnetic resonance imaging. Performance on a go-nogo task inside the scanner.

  Baseline and 8 weeks

Secondary Outcomes (6)

• Clinical Global Impressions (CGI-I)

  up to 8 weeks

• Percentage Change in Atomoxetine Stimulant Side Effects Rating Scale (ASSERS)

  up to 8 weeks

• Finger Windows

  Baseline

• Digit Span

  Baseline

• Attention Deficit Hyperactivity Disorder Rating Scale IV (ADHDRS IV)

  baseline and 8 weeks

Study Arms (2)

guanfacine hydrochloride XR

EXPERIMENTAL

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

Placebo Group

PLACEBO COMPARATOR

Flexible dose titration of placebo

Drug: Placebo

Interventions

Guanfacine Hydrochloride XR DRUG

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Also known as: INTUNIV non-stimulant medication, GXR

guanfacine hydrochloride XR

Placebo DRUG

Weekly adjustments based on parent ratings of symptoms, side effects, and health status per vital signs up to 4mg maximum dose

Placebo Group

Eligibility Criteria

• Age: 8 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (1)

• 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.

  PMID: 25659477 RESULT

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

The small sample size in this pilot study limited power to detect large-sized effects.

Results Point of Contact

• Title: Department of Psychiatry
• Organization: Icahn School of Medicine at Mount Sinai

212-241-6623

Study Officials

• Jeffrey Newcorn, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: October 18, 2012
• Study Start: March 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: February 14, 2018
• Results First Posted: February 14, 2018

Record last verified: 2018-01

Locations

US (1)