Attention Deficit Disorder With Hyperactivity
Conditions
Keywords
Attention Deficit Disorder with Hyperactivity, Attention Deficit Hyperactivity Disorder, ADHD
Brief summary
A number of brain regions have been down to be altered in both structure and function in patients with ADHD, including prefrontal cortex, anterior cingulate, caudate and cerebellum. Patients with ADHD often show reduced levels of activity in the frontal and cingulate regions of brain while performing measures of inhibitory control during functional magnetic resonance imaging (fMRI). While stimulant medications robustly improve the clinical symptoms of ADHD, there are only a small number of studies examining the effects of these commonly prescribed medications on brain activity. We propose to obtain fMRI in patients with ADHD on placebo and on their individualized dose of OROS methylphenidate (Concerta). Our hypothesis is that Concerta will increase the activity of the brain in the frontal, cingulate and amygdala of the brain and that these brain changes will be associated with clinical improvement of symptoms.
Detailed description
Three age groups of subjects will be studied: school age children (aged 9-12), older adolescents (age 15-17 years) and young adults (age 20-25 years). Twenty subjects will be studied in each group. All subjects must meet criteria for ADHD, combined type and be either treatment naïve or currently taking and responding well to Concerta. Child and adolescent patients taking Concerta will have their current levels of ADHD symptoms assessed with the Dupaul ADHD rating scale (11); adults taking Concerta will be assessed with Conners Adult ADHD Rating Scale (CAARS). Patients whose symptoms are in remission as evidenced by scores in the normal range on these scales may proceed directly to the neuroimaging portion of the study. Subjects who are treatment naïve or are treated but are not in remission shall under a three week open label trial of Concerta to determine the optimal dose for treatment of their symptoms. Subjects will have two fMRI sessions on different days. During each fMRI session, they will perform both the Stop Signal Task and the Emotional Conflict Resolution Task . On the morning of the scan, placebo and Concerta will be administered in a double-blind, crossover design, with order of medication and placebo randomized. The scan sessions will take place between 3 and 7 hours after medication administration. After each scan, the subject and a research assistant will go to a quiet room in the imaging center; the subjects will be given arithmetic level set at a level of difficulty that the subject has mastered. The subject will be given 15 minutes to complete as many problems as possible.
Interventions
DRUGmethylphenidate-OROS
The collaborator (Ortho-McNiel Janssen Scientific Affairs, LLC) will provide capsules of Concerta that are made to appear similar to placebo capsules. The subject will be administered their usual dose of Concerta the morning of the scan.
DRUGPlacebo
The collaborator (Ortho-McNiel Janssen Scientific Affairs, LLC) will provide capsules of placebo that are made to appear similar to Concerta capsules. The subject will be administered placebo the morning of the scan.
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Meets DSM-IV criteria for Attention Deficit Hyperactivity Disorder * Current clinical responder to Concerta (OROS-methylphenidate)
Exclusion criteria
* IQ \< 95 * Presence of Learning Disorder * Presence of an Affective or Psychotic Disorder * Presence of a Substance/Alcohol Abuse/Dependence Disorder * Presence of an Autism Spectrum Disorder * Presence of a Tic Disorder * Taking any psychotropic medication other than Concerta * A medical condition requiring daily medication * Previous adverse or non response to Concerta
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Placebo and Drug day, 1-2 weeks apart | Each subject viewed shapes and faces on multiple trials. The subject matched faces or shapes on each trial. BOLD activity during shape trials was subtracted from BOLD activity during Face trials and this value was compared on drug vs. placebo trials. |
Countries
United States
Participant flow
Recruitment details
A total of 75 patients were enrolled from 11/4/2008 t0 8/12/2010. Patients were recruited from advertisements in local papers as well as flyers in the UTHSCSA psychiatric clinic.
Pre-assignment details
Psychiatric assessment was performed to confirm the diagnosis of ADHD. Fifteen (15) patients were screen failures. Five (5) patients did not respond to an open label trial of Concerta were excluded. 11 withdrew consent or lost to follow up. (1) withdrew to claustrophobia. 43 were exposed to study drug (Concerta and placebo) in crossover design.
Participants by arm
| Arm | Count |
|---|---|
| Adults These were participants between the age of 21-25 years. They underwent 2 FMRI studies, once on placebo and once on Concerta in a double blind randomized crossover design. | 17 |
| Children These were participants between the age of 3- 17 years. They underwent 2 FMRI studies, once on placebo and once on Concerta in a double blind randomized crossover design. | 26 |
| Total | 43 |
Baseline characteristics
| Characteristic | Children | Adults | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 26 Participants | 0 Participants | 26 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 17 Participants | 17 Participants |
| Age Continuous | 11.3 years STANDARD_DEVIATION 2.1 | 22.2 years STANDARD_DEVIATION 1.78 | 15.6 years STANDARD_DEVIATION 5.7 |
| Region of Enrollment United States | 26 participants | 17 participants | 43 participants |
| Sex: Female, Male Female | 8 Participants | 2 Participants | 10 Participants |
| Sex: Female, Male Male | 18 Participants | 15 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 26 |
| serious Total, serious adverse events | 0 / 17 | 0 / 26 |
Outcome results
Primary
Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo
Each subject viewed shapes and faces on multiple trials. The subject matched faces or shapes on each trial. BOLD activity during shape trials was subtracted from BOLD activity during Face trials and this value was compared on drug vs. placebo trials.
Time frame: Placebo and Drug day, 1-2 weeks apart
Population: The number who completed both fMRI one week apart (crossover study, scanned twice
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Adults Drug Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Amygdala | 1.79 Face-Shape BOLD signal difference | Standard Deviation 1.06 |
| Adults Drug Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Fusiform Gyrus | 1.46 Face-Shape BOLD signal difference | Standard Deviation 1.36 |
| Adults Placebo Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Fusiform Gyrus | 1.64 Face-Shape BOLD signal difference | Standard Deviation 1.21 |
| Adults Placebo Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Amygdala | 0.58 Face-Shape BOLD signal difference | Standard Deviation 1.09 |
| Children Drug Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Amygdala | 1.43 Face-Shape BOLD signal difference | Standard Deviation 1.08 |
| Children Drug Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Fusiform Gyrus | 1.99 Face-Shape BOLD signal difference | Standard Deviation 1.1 |
| Children Placebo Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Amygdala | 0.77 Face-Shape BOLD signal difference | Standard Deviation 1.36 |
| Children Placebo Condition | Brain Oxygenation Level Dependent Signal in the Fusiform Gyrus and the Amygdala on Concerta vs. Placebo | Fusiform Gyrus | 1.06 Face-Shape BOLD signal difference | Standard Deviation 1.12 |