Neuroimaging of the Effects of Concerta in the Treatment of ADHD

Attention Deficit Disorder With Hyperactivity Clinical Trial

Official title:

Functional Neuroimaging of Acute Concerta Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): Differences Across Development

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00778310
• Other study ID #: CONCERTAATT4087
• Status: Completed
• Phase: Phase 4
• First received: October 22, 2008
• Last updated: June 8, 2012
• Start date: November 2008
• Est. completion date: December 2010

Study information

• Verified date: April 2012
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 9 Years to 25 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)

Related Conditions & MeSH terms

• Attention Deficit Disorder With Hyperactivity
• Hyperkinesis

Intervention

Drug:
• methylphenidate-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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Dept of Psychiatry, UTHSCSA	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	Ortho-McNeil Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bush G, Spencer TJ, Holmes J, Shin LM, Valera EM, Seidman LJ, Makris N, Surman C, Aleardi M, Mick E, Biederman J. Functional magnetic resonance imaging of methylphenidate and placebo in attention-deficit/hyperactivity disorder during the multi-source interference task. Arch Gen Psychiatry. 2008 Jan;65(1):102-14. doi: 10.1001/archgenpsychiatry.2007.16. — View Citation

Pliszka SR, Glahn DC, Semrud-Clikeman M, Franklin C, Perez R 3rd, Xiong J, Liotti M. Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment. Am J Psychiatry. 2006 Jun;163(6):1052-60. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Placebo and Drug day, 1-2 weeks apart	No