Lisdexamfetamine's Effect In ADHD in the Brain and Cognition (LEIA)
The purpose of this study is to identify the effects of lisdexamfetamine (LDX) on the neural and behavioral subcomponents of self-control, that is cognitive control and reward functioning, in adolescents and young adults with attention-deficit/hyperactivity disorder.
The investigators hypothesize that LDX is associated with 1a) decreased task-independent locus coeruleus (LC) activity; 1b) increased task-related activity in LC and the cognitive control network; 2) increased LC connectivity with the cognitive control network and 3) improved task performance and self-control. The investigators will test their hypotheses on fMRI data with linear contrasts of voxel-wise maps of parameter estimates (in both univariate and connectivity analyses).
The investigators will also assess change in brain activity with the LDX in the LC and ventral tegmental areas (VTA) as we hypothesize that they are altered in ADHD and related to cognitive control and self-control dysfunction in ADHD.
The investigators will use a repeated-measures, between-subject design to compare the effects of oral once daily LDX in a double-blind placebo-controlled randomized trial (RCT) on neural (fMRI) and behavioral correlates of cognitive control via a working memory and a reward - delay discounting task in adolescents and young adults.
Attention Deficit Hyperactivity Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
|Official Title:||Effects of Lisdexamfetamine on Cognitive Control and Reward Response in Adolescents and Young Adults With ADHD: Neural and Clinical Outcomes|
- Primary Neural Endpoints [ Time Frame: The effects of the medication versus placebo will be assessed after 8 weeks of treatment (or placebo) ] [ Designated as safety issue: No ]To evaluate the effects of Lisdexamfetamine on a) task-related regional brain activity (i.e., working memory versus self-control associated brain regions).
- Primary Cognitive Outcome [ Time Frame: Compare baseline to 8 weeks after begin medication or placebo ] [ Designated as safety issue: No ]To evaluate the effects of Lisdexamfetamine on working memory performance and degree of self-control on the delay discounting task after optimal dose is achieved and 8 weeks of treatment, in comparison to baseline and placebo
- Secondary Task and Cognitive Measures [ Time Frame: Baseline versus 8 weeks after starting on lisdesxamfetamine or placebo. ] [ Designated as safety issue: No ]Assess the effects of Lisdexamfetamine on risk taking as assessed by a computerized risk taking task.
- Task-related brain connectivity [ Time Frame: 8 weeks after medication (or placebo) in comparison to baseline ] [ Designated as safety issue: No ]Connectivity between cognitive control and reward related brain regions will be compared between active treatment versus placebo.
- Personalized daily goal changes [ Time Frame: Baseline versus 8 weeks into the medication (or placebo). ] [ Designated as safety issue: No ]Assess the effects of LDX on successful completion on individualized and personalized daily goals.
- ADHD Ratings - ASRS [ Time Frame: Baseline and 8 weeks after the subject is randomized to placebo or medication ] [ Designated as safety issue: No ]ADHD ratings of behavior.
- Automobile driving [ Time Frame: Baseline and 8 weeks after randomized to placebo or medication. ] [ Designated as safety issue: No ]Assessment of automobile driving for persons who are old enough to drive using the Barkley Driving Scale.
- Executive functioning [ Time Frame: Baseline and 8 weeks after randomization to placebo or active condition ] [ Designated as safety issue: No ]Measures of executive functioning, including the BRIEF and other similar measures.
- Quality and type of interaction measures [ Time Frame: Baseline and 8 weeks after randomized to placebo or medication condition. ] [ Designated as safety issue: No ]Qualify of life and functional behavioral measures.
- Pupillometry Measures Collected During fMRI Acquisition [ Time Frame: Baseline versus 8 weeks after start medication or placebo. ] [ Designated as safety issue: No ]We will assess for changes in pupil dynamics, including how pupil diameter may work as a marker to assess medication response.
- Clinical Global Impression Ratings [ Time Frame: Baseline compared to 8 weeks after start in trial. ] [ Designated as safety issue: No ]Assess for changes in the Clinical Global Impression Ratings
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
Participants may be randomized into the placebo comparator arm. Participants in this group will be given a sugar pill titrated up to 70 mg daily over the course of 9 weeks.
Participants may be randomized into the experimental arm. Participants in this arm will be given lisdexamfetamine titrated up to 70 mg daily over the course of 9 weeks.
Participants will be given either the study drug or placebo in tablet form. All participants will start with a 20 mg dose and will be titrated up to a 70 mg daily dose over 9 weeks. Participants between 12-18 years of age will be titrated in 10 mg increments and participants between 18-25 years of age in 20 mg increments.
Other Name: Vyvanse
Please refer to this study by its ClinicalTrials.gov identifier: NCT02170298
|Contact: Cynthia Krafft, PhD||916 703 0231||Cynthia.email@example.com|
|Contact: Tadeus A Hartanto, BS||916 703 firstname.lastname@example.org|
|United States, California|
|UC Davis MIND Institute||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Cynthia Krafft, PhD 916-703-0231 Cynthia.Krafft@ucdmc.ucdavis.edu|
|Contact: Tadeus A Hartanto, BS 916 703 0294 email@example.com|
|Principal Investigator: Julie B Schweitzer, PhD|
|Principal Investigator:||Julie B Schweitzer, PhD||University of California, Davis|