An fMRI Study of Stimulant vs. Non-Stimulant Treatment of ADHD

Imaging Stimulant vs. Non-Stimulant Treatment of Attention Deficit Hyperactivity Disorder (ADHD)

Children with Attention-Deficit/Hyperactivity Disorder (ADHD) are typically treated with two types of medications with differing mechanisms of action: stimulants and non-stimulants. The stimulant Vyvanse (lisdexamfetamine, LDX), and the non-stimulant Intuniv (extended-release guanfacine, GXR), are both FDA approved treatment for ADHD. Clinical trials have shown that both medications are effective in reducing ADHD symptoms, although the neurobiological mechanisms by which Vyvanse and Intuniv produce these effects remain unknown. The aim of this study is to examine the mechanisms by which LDX and GXR reduce symptoms in patients with ADHD. MRI scanning will be used to identify treatment-related changes in brain structure and function.

Study Overview

• Status: Completed
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Drug: Guanfacine; Drug: Lisdexamfetamine

Detailed Description

Children with ADHD and age and sex-matched healthy controls will be scanned at the beginning of the study. In this first part of the study, MRI findings will be compared between the two groups to see whether brain functioning of children with ADHD differs from that of healthy children. In the second part of the study, the children with ADHD will meet weekly with the study doctor and be administered either extended-release guanfacine (Intuniv) or lisdexamfetamine (Vyvanse) for 6 weeks. Selection into either treatment group will be randomly determined. At the end of the study, the children with ADHD treated with either medication will have a second MRI scan. The findings of that second MRI scan will be compared to the first MRI scan in order to examine brain changes due to the medication. These second MRI scans will also be compared to the scans of the healthy controls.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

ADHD Participants:

• The participant satisfies Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for a primary diagnosis of ADHD, any subtype.

Healthy Control Participants:

• The participant must have no current DSM Axis I psychiatric disorder.

All Participants:

• Participants must provide assent and a legal guardian must provide consent.
• The participant is male or female and between 6 - 17 years of age and in good physical health.
• Girls of childbearing potential must have a negative urine pregnancy test and, if sexually active, must be using adequate contraception.
• The participant is English speaking.

Exclusion Criteria:

ADHD Participants:

• The participant has a current comorbid DSM Axis I psychiatric diagnosis or other symptomatic manifestations that, in the opinion of the study doctor, will contraindicate lisdexamfetamine or guanfacine treatment or confound safety assessments.
• The participant meets DSM-5 criteria for current substance abuse and/or dependence.
• The participant is currently taking or has taken within the past 4 months, a psychotropic medication.
• The participant has a documented allergy or intolerance to lisdexamfetamine or guanfacine products.
• The participant has a diagnosis or a history of cardiovascular disease or any other serious medical illness.
• The participant is pregnant or lactating.
• The participant is actively suicidal.
• MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces)
• The participant has a full-scale intelligence quotient (IQ) less than 70.
• The participant has a history of seizure (except febrile seizure).

Healthy Controls:

• The participant meets DSM criteria for current substance abuse and/or dependence.
• The participant is currently taking a psychotropic medication.
• The participant has a history of a serious medical illness.
• The participant is pregnant or lactating.
• MRI contraindications (e.g., irremovable metal on the body, pacemaker, braces)
• The participant has a full-scale intelligence quotient (IQ) less than 70.
• The participant has a history of seizure (except febrile seizure).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Guanfacine; Participants will be administered extended-release guanfacine, which is in tablet form, and will be instructed to take the medication once daily for 6 weeks. The daily dose will range between 1 and 4 mg.	Drug: Guanfacine; Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.; Other Names: Intuniv; GXR
Experimental: Lisdexamfetamine; Participants will be administered lisdexamfetamine, which is in tablet form, and will be instructed to take the medication daily for 6 weeks. The daily dose will range between 30 and 70mg.	Drug: Lisdexamfetamine; Participants will meet with the study doctor on a weekly basis during the treatment phase of the study. In the first few weeks, the daily dose of the medication will be individually adjusted by the study doctor according to participants' clinical response to and tolerability of the medication. The optimal dose will then be maintained for the remainder of the treatment period.; Other Names: Vyvanse; LDX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in brain structure and function produced by stimulant or non-stimulant medications in patients with ADHD	MRI (Magnetic Resonance Imaging)	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: Columbia University; Shire; American Academy of Child Adolescent Psychiatry.
• Investigators: Principal Investigator: Jonathan Posner, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): November 6, 2021
• Study Completion (Actual): November 6, 2021

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 8, 2014

Study Record Updates

• Last Update Posted (Actual): December 14, 2021
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: ADHD; Stimulant; Non-stimulant; Intuniv; Guanfacine extended-release; Vyvanse; Lisdexamfetamine
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Attention Deficit Disorder with Hyperactivity; Hyperkinesis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate; Guanfacine
• Other Study ID Numbers: 6961

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No