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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
ADHD

Intervention / Treatment
-----------------
* Drug: Lisdexamfetamine


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Attention Deficit Hyperactivity Disorder, ADHD, fMRI, Imaging, Vyvanse, Stimulant Medication, Treatment, Clinical Trial, Adult