Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation

The purpose of this study is to determine the effects of Vyvanse, an FDA approved medication used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), on brain activity in adults with attention-deficit hyperactivity disorder (ADHD). Participants may qualify for participation in this study because they have ADHD and are willing to participate in two Functional Magnetic Resonance Imaging (fMRI) scans and receive Vyvanse for treatment of their symptoms. Another purpose of this study is to collect and bank samples of blood for research to examine how genes influence brain activation seen during the brain scans. The study also seeks to find out whether certain genes are related to ADHD. Participants' entire genetic makeup will not be determined from this sample.

Study Overview

• Status: Completed
• Conditions: ADHD
• Intervention / Treatment: Drug: Lisdexamfetamine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • ICAHN School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary DSM-IV-TR diagnosis of adult ADHD (inattentive, hyperactive-impulsive or combined subtype), established via the ACDS v1.2.
• Must be between 18-55 years, inclusive.
• Provides written informed consent.

Exclusion Criteria:

• Lifetime or current diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder.
• Current diagnosis of comorbid major depressive disorder, anxiety disorder or dysthymia or any controlled (i.e. requires pharmacological treatment) comorbid diagnosis. Participants with uncontrolled depressive or anxiety disorders may participate if, in the opinion of the Principal Investigator, the disorder will not confound the results of efficacy or safety assessments, increase risk to the participant or lead to difficulty complying with the protocol.
• Meets current DSM-IV-TR criteria for alcohol or any non-alcohol substance abuse or dependence disorder.
• Have organic brain disease (such as dementia) or traumatic brain injury residua. Have a history of seizure disorder (other than febrile seizures) or participants who have taken (or are currently taking) anticonvulsants for seizure control.
• Females who are currently pregnant or breast feeding, and women of child-bearing potential who are not currently using an adequate form of birth control.
• Participants with clinically significant abnormalities in ECG results that are deemed exclusionary in the opinion of the Principal Investigator will not be allowed in the trial.
• Participants who work the night shift or another schedule that would preclude beginning the daily dose of study medication in the morning.
• Participants with a positive urine drug result at Screening.
• Medical conditions limiting participation in the study.
• Documented history of intolerance or non-responsivity to methylphenidate or amphetamines.
• Have a medical condition that would, in the opinion of the study physician, make participation medically hazardous.
• ADHD, Not Otherwise Specified
• History of surgery involving metal implants, metal fragments in the eyes, braces, or a pacemaker.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: On Drug then off Drug; Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg	Drug: Lisdexamfetamine; Escalating stepped dose titration: 30, 50 or 70mg; Other Names: Vyvanse
Experimental: Off drug then on drug; Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg	Drug: Lisdexamfetamine; Escalating stepped dose titration: 30, 50 or 70mg; Other Names: Vyvanse

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Go/No-Go Task Percentage Assessed by fMRI	Performance Measures on the Go/No-Go Task assessed by fMRI as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder. The Go/No-Go Task is a neuropsychological test that provides a direct measure of number of responses made that are "correct" or "incorrect". It is not a scale. Reported are the percentage of correct responses on that direct performance measure. 0% correct is worse than 100% correct.	8 weeks
fMRI Reaction Time	Reaction-time, as measured by the reaction time test Go/No-Go Task as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder	up to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BRIEF-A	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (0 to 100, with 50 +/-1 SD = 'Normal', higher is worse, more impaired)	Baseline
BRIEF-A	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)	at one week
BRIEF-A	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)	at 4 weeks
ASRS - Expanded	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).	Baseline
ASRS - Expanded	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).	at one week
ASRS - Expanded	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).	at 4 weeks
WRAADS	The Wender-Reimherr adult attention deficit disorder scale (WRAADS): Symptom measure for emotional functioning/lability, generally reported as Sum of Responses (0-2 per item, higher = more impaired). For this outcome measure, Average scores for particular questions were taken - specifically question 3, question 4, and question 5.	Baseline
ADHD-RS-IV Combined Sum	ADHD symptoms and severity. Norm referenced interview to assess severity and frequency of ADHD symptoms. 18 Items are scored 0-3 to reflect severity and frequency of ADHD symptoms, and a sum is taken. Full range from 0 to 54, with higher number indicating more symptoms and severity.	Baseline
ADHD-Inattentive	ADHD symptoms and severity - subscale for Inattentiveness. 9-item scale, each scored 0-3, with total from 0 to 27. Higher score indicates higher level of inattentiveness.	4 weeks and 8 weeks
CGI-I	Clinical Global Impressions - CGI-I: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse).	Baseline
CGI-S	CGI-S: Severity of impairment due to ADHD was measured by the Clinical Global Impressions-Severity scale (CGI-S). Lower scores indicate less severe impairment from symptoms, with a CGI-I=1 indicating the person is "normal" with no impairment. (1= normal, not ill, 2= minimally ill, 3= mildly ill, 4= moderately ill, 5=markedly ill, 6=severely ill, 7= very severely ill)	baseline

Collaborators and Investigators

• Sponsor: Jeffrey Newcorn

Publications and helpful links

General Publications

• Schulz KP, Krone B, Adler LA, Bedard AV, Duhoux S, Pedraza J, Mahagabin S, Newcorn JH. Lisdexamfetamine Targets Amygdala Mechanisms That Bias Cognitive Control in Attention-Deficit/Hyperactivity Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Aug;3(8):686-693. doi: 10.1016/j.bpsc.2018.03.004. Epub 2018 Mar 19.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 14, 2013
• First Submitted That Met QC Criteria: August 15, 2013
• First Posted (Estimate): August 16, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Treatment; Imaging; ADHD; Attention Deficit Hyperactivity Disorder; fMRI; Adult; Clinical Trial; Vyvanse; Stimulant Medication
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Lisdexamfetamine Dimesylate
• Other Study ID Numbers: GCO 09-1186