Attention Deficit Disorder With HyperactivityNCT00104039
Brain Changes in Children and Adolescents With Behavioral Problems
An observational study of Attention Deficit Disorder With Hyperactivity and Mental Disorders Diagnosed in Childhood, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Purpose: This study will examine brain activity in children age 10-18 with disruptive behavior problems, including conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD), compared with children without behavioral problems. Read more about this study
- Who is it for?
- Ages 8 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Disorder With Hyperactivity, Mental Disorders Diagnosed in Childhood, Conduct Disorder
- How many people
- 318 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2005to 21 Jul 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Individuals with CD + CU: Male and female subjects aged 8-18 who score equal to or more than 20 on the APSD/PCL-YV. Children with antisocial behavioral problems on medications with psychotropic effects will be considered if their target behaviors persist despite the use of medications. In these children, only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivatives including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), modafinil (Provigil), or valproic acid (Depakote), or other mood stabilizers are not safe to stop suddenly and children taking these medications will not be asked to stop them.
- Individuals with CD-CU: Male and female subjects aged 8 -18 who score less than 20 on the APSD/PCL-YV. Children with antisocial behavioral problems on medications with psychotopic effects will be considered if their target behaviors persist despite the use of medications. In these children, only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivatives including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate-CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin Medications like Starattera (atomoxetine), bupropion (Wellbutrin), modafinil (Provigil), or valproic acid (Depakote), or other mood stabilizers are not safe to stop suddenly and children taking these medications will not be asked to stop them.
- Individuals with ADHD: Male and female subjects aged 8-18 who currently meet DSM-IV criteria for ADHD. The diagnosis will be made on the basis of a K-SADS-PL interview with the parent and a t score >65 on the hyperactivity-impulsivity subscale of the Connors Teacher Scale. Participants in this group will have APSD scores <20.
- Comparison individuals: Male and female subjects aged 8-18 who are free from any current or past psychopathology (all will score less than 20 on the APSD/PCL-YV).
Who cannot join
- I.Q.< 75.
- Ongoing medical illness other than those listed in the inclusion criteria for the respective groups that require use of any medication that may have psychotropic effects. For example, a patient with history of mild asthma that did not require medication may be included, however a patient with asthma requiring use of beta blockers, steroids, etc. would not be included. For children with ADHD or healthy volunteer children, a contraindication to discontinuing medication for 48 hours. Only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivative including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), or modafinil (Provigil) are not safe to stop suddenly and children with ADHD taking these medications will not be included.
- Subjects with psychopathic tendencies who receive a diagnosis of an anxiety or mood disorder as determined by a clinical and K-SAD review conducted by a psychiatrist will be excluded. Additionally, children with active psychosis, pervasive developmental disorders or Tourette s syndrome will be excluded.
- Children with CD-CU will be evaluated through the KSAD and clinical review by a psychiatrist. Explicit exclusions include active psychosis, Pervasive Developmental Disorders and Tourette s syndrome. Children with anxiety disorders will be included given the high comorbidity of CD-CU and anxiety disorders.
- Individuals with ADHD will be evaluated through the KSAD and clinical review by a psychiatrist. Those children who receive diagnosis of mood disorders through this evaluation process will be excluded. Additional explicit exclusions include active psychosis, Pervasive Developmental Disorders and Tourette s syndrome. Children with anxiety disorders will be included given the high comorbidity of ADHD and anxiety disorders.
- Any other psychiatric disorder that is sufficiently severe to require specific treatment, with the exception of those listed in the inclusion criteria for the respective groups.
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- Neurologic disorder (including seizures).
- Any metallic objects in the body. Metal plates, certain types of dental braces, cardiac pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI scans.
- Claustrophobia: participants will be questioned about potential discomfort in being in an enclosed space, such as an MRI scanner.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Investigating the Neuro-Cognitive Underpinnings of the Emotional Dysfunction Linked to Childhood Behavioral Disturbance
Purpose:
This study will examine brain activity in children age 10-18 with disruptive behavior problems, including conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD), compared with children without behavioral problems. Our goal is to examine differences in how emotions, social situations, and problem-solving situations are processed in the brain across these groups of children.
Read the detailed description
OBJECTIVE:
The goal of this protocol is to investigate the neuro-cognitive underpinnings of the emotional dysfunction linked to childhood behavioral disturbance; in particular, Conduct Disorder with elevated callous-unemotional (CU) traits (CD+CU), Conduct Disorder with non elevated CU traits (CD-CU), but also ADHD. The functional hypotheses that we are testing with both neuro-cognitive and neuro-imaging paradigms are that: (1) CD+CU, but not ADHD, is associated with dysfunction in the formation and operational use of stimulus-punishment and, to a lesser extent, stimulus-reward association information; (2) CD-CU is associated with heightened threat sensitivity and impairment in executive systems involved in emotional regulation; and (3) that ADHD and CD-CU, is associated with impairment in executive systems related to the representation and execution of task demands.
STUDY POPULATION:
160 children with Conduct Disorder (CD) and high CU traits (the CD+CU group); 160 children with CD and low CU traits (the CD-CU group); 160 children with ADHD; and 160 healthy volunteer children. All children will be between the ages of 10 and 17. Both males and females will be enrolled.
DESIGN:
The current study will have two phases: i) neuropsychological assessment and training in an MRI simulator (up to 4 hours); ii) The MRI scanning session (up to 2 hours, no more than 90 minutes in scanner). Participants, if they are willing, may be invited to participate in more than one scanning session (up to a maximum of 3 120 minute sessions) or neuro-cognitive testing session.
OUTCOME MEASURES:
Behaviorally, we predict that children with CD+CU and children with CD-CU will present with impairment on tasks that involve either the formation or operational use of particular stimulus-punishment associations (e.g., the subjective value learning task and emotional interrupt task). However, the nature of this impairment with be qualitatively different. For example, we predict that youth with CD+CU will show reduced interference by emotional distracters on the emotional interrupt task but that youth with CD-CU will show decreased interference. In contrast, we predict that children with ADHD, but no CD, will show no behavioral impairment on such tasks. However, we predict that children with ADHD and children with CD-CU will present with impairments on executive function tasks (e.g., the Number Stroop paradigm). In contrast, we predict that children with CD+CU will show no impairment on these tasks. At the anatomical level, we anticipate reduced activation of emotional related systems in children with CD+CU, but increased activation in children with CD-CU, during emotional impact tasks (in particular, reduced activation of the amygdala, regions of orbitofrontal cortex and anterior cingulate). We anticipate that the neural response of children with ADHD during these tasks will be less anomalous. We anticipate that the neural response of children with ADHD and children with CD-CU during the performance of response control tasks to be anomalous (with considerable greater recruitment of anterior and posterior compensatory systems).
- Conditions
- Attention Deficit Disorder With Hyperactivity, Mental Disorders Diagnosed in Childhood, Conduct Disorder
- Keywords
- Amygdala, Orbital Frontal Cortex, Serotonin, Orbitofrontal Cortex, Attention Deficit Hyperactivity Disorder, ADHD, Anti-Social Behavior, Healthy Volunteer, HV
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Neurodevelopmental Disorders, Conduct Disorder, Antisocial Personality Disorder
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2005 (estimated)
- Study start17 Feb 2005
- Study completion21 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Disorder With HyperactivityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James J Blair, Ph.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00104039
- Sponsor's protocol ID
- 050105
- Other IDs
- 05-M-0105
- Status last verified
- 21 Jul 2016
- First submitted
- 19 Feb 2005
- Last updated
- 5 Nov 2019
- Results posted
- No
Publications
Ambrogi Lorenzini CG, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Neural topography and chronology of memory consolidation: a review of functional inactivation findings. Neurobiol Learn Mem. 1999 Jan;71(1):1-18. doi: 10.1006/nlme.1998.3865.
PubMed 9889069Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. doi: 10.1038/nn1003. No abstract available.
PubMed 12536210Babinski LM, Hartsough CS, Lambert NM. Childhood conduct problems, hyperactivity-impulsivity, and inattention as predictors of adult criminal activity. J Child Psychol Psychiatry. 1999 Mar;40(3):347-55.
PubMed 10190336Hwang S, Meffert H, Parsley I, Tyler PM, Erway AK, Botkin ML, Pope K, Blair RJR. Segregating sustained attention from response inhibition in ADHD: An fMRI study. Neuroimage Clin. 2019;21:101677. doi: 10.1016/j.nicl.2019.101677. Epub 2019 Jan 15.
PubMed 30682530Tyler PM, White SF, Thompson RW, Blair RJR. Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools. Dev Neuropsychol. 2019 Jan-Feb;44(1):17-42. doi: 10.1080/87565641.2017.1334782. Epub 2018 Feb 12.
PubMed 29432037White SF, Thornton LC, Leshin J, Clanton R, Sinclair S, Coker-Appiah D, Meffert H, Hwang S, Blair JR. Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders. J Abnorm Child Psychol. 2018 May;46(4):741-754. doi: 10.1007/s10802-017-0335-0.
PubMed 28776147White SF, VanTieghem M, Brislin SJ, Sypher I, Sinclair S, Pine DS, Hwang S, Blair RJ. Neural Correlates of the Propensity for Retaliatory Behavior in Youths With Disruptive Behavior Disorders. Am J Psychiatry. 2016 Mar 1;173(3):282-90. doi: 10.1176/appi.ajp.2015.15020250. Epub 2015 Oct 6.
PubMed 26441155
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Neuro-Cognitive Underpinnings of the Emotional Dysfunction Linked to Childhood Behavioral Disturbance
- ClinicalTrials.gov ID
- NCT00104039
- Acronym / sponsor ID
- 050105
- Conditions
- Attention Deficit Disorder With Hyperactivity, Mental Disorders Diagnosed in Childhood, Conduct Disorder
- Keywords
- Amygdala, Orbital Frontal Cortex, Serotonin, Orbitofrontal Cortex, Attention Deficit Hyperactivity Disorder, ADHD, Anti-Social Behavior, Healthy Volunteer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 17 Feb 2005
- Study completion
- 21 Jul 2016
- First posted
- 21 Feb 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose:
This study will examine brain activity in children age 10-18 with disruptive behavior problems, including conduct disorder (CD), oppositional defiant disorder (ODD), and attention deficit hyperactivity disorder (ADHD), compared with children without behavioral problems. Our goal is to examine differences in how emotions, social situations, and problem-solving situations are processed in the brain across these groups of children.
Detailed description
OBJECTIVE:
The goal of this protocol is to investigate the neuro-cognitive underpinnings of the emotional dysfunction linked to childhood behavioral disturbance; in particular, Conduct Disorder with elevated callous-unemotional (CU) traits (CD+CU), Conduct Disorder with non elevated CU traits (CD-CU), but also ADHD. The functional hypotheses that we are testing with both neuro-cognitive and neuro-imaging paradigms are that: (1) CD+CU, but not ADHD, is associated with dysfunction in the formation and operational use of stimulus-punishment and, to a lesser extent, stimulus-reward association information; (2) CD-CU is associated with heightened threat sensitivity and impairment in executive systems involved in emotional regulation; and (3) that ADHD and CD-CU, is associated with impairment in executive systems related to the representation and execution of task demands.
STUDY POPULATION:
160 children with Conduct Disorder (CD) and high CU traits (the CD+CU group); 160 children with CD and low CU traits (the CD-CU group); 160 children with ADHD; and 160 healthy volunteer children. All children will be between the ages of 10 and 17. Both males and females will be enrolled.
DESIGN:
The current study will have two phases: i) neuropsychological assessment and training in an MRI simulator (up to 4 hours); ii) The MRI scanning session (up to 2 hours, no more than 90 minutes in scanner). Participants, if they are willing, may be invited to participate in more than one scanning session (up to a maximum of 3 120 minute sessions) or neuro-cognitive testing session.
OUTCOME MEASURES:
Behaviorally, we predict that children with CD+CU and children with CD-CU will present with impairment on tasks that involve either the formation or operational use of particular stimulus-punishment associations (e.g., the subjective value learning task and emotional interrupt task). However, the nature of this impairment with be qualitatively different. For example, we predict that youth with CD+CU will show reduced interference by emotional distracters on the emotional interrupt task but that youth with CD-CU will show decreased interference. In contrast, we predict that children with ADHD, but no CD, will show no behavioral impairment on such tasks. However, we predict that children with ADHD and children with CD-CU will present with impairments on executive function tasks (e.g., the Number Stroop paradigm). In contrast, we predict that children with CD+CU will show no impairment on these tasks. At the anatomical level, we anticipate reduced activation of emotional related systems in children with CD+CU, but increased activation in children with CD-CU, during emotional impact tasks (in particular, reduced activation of the amygdala, regions of orbitofrontal cortex and anterior cingulate). We anticipate that the neural response of children with ADHD during these tasks will be less anomalous. We anticipate that the neural response of children with ADHD and children with CD-CU during the performance of response control tasks to be anomalous (with considerable greater recruitment of anterior and posterior compensatory systems).
Study design
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
Key exclusion criteria (9 listed)
- I.Q.< 75.
- Ongoing medical illness other than those listed in the inclusion criteria for the respective groups that require use of any medication that may have psychotropic effects. For example, a patient with history of mild asthma that did not require medication may be included, however a patient with asthma requiring use of beta blockers, steroids, etc. would not be included. For children with ADHD or healthy volunteer children, a contraindication to discontinuing medication for 48 hours. Only simple stimulant medications will be held for 48 hours. These include methylphenidate, amphetamine and their derivative including Ritalin, Ritalin SR, Ritalin LA, Methylin, Methlin ER, Metadate CD, Concerta, Dexedrine, Dextrostat, Dexedrine Spansule, Adderall, Adderall XR, and Focalin. Medications like Strattera (atomoxetine), bupropion (Wellbutrin), or modafinil (Provigil) are not safe to stop suddenly and children with ADHD taking these medications will not be included.
- Subjects with psychopathic tendencies who receive a diagnosis of an anxiety or mood disorder as determined by a clinical and K-SAD review conducted by a psychiatrist will be excluded. Additionally, children with active psychosis, pervasive developmental disorders or Tourette s syndrome will be excluded.
- Children with CD-CU will be evaluated through the KSAD and clinical review by a psychiatrist. Explicit exclusions include active psychosis, Pervasive Developmental Disorders and Tourette s syndrome. Children with anxiety disorders will be included given the high comorbidity of CD-CU and anxiety disorders.
- Individuals with ADHD will be evaluated through the KSAD and clinical review by a psychiatrist. Those children who receive diagnosis of mood disorders through this evaluation process will be excluded. Additional explicit exclusions include active psychosis, Pervasive Developmental Disorders and Tourette s syndrome. Children with anxiety disorders will be included given the high comorbidity of ADHD and anxiety disorders.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2019.
- Background: PubMed 9889069Ambrogi Lorenzini CG, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Neural topography and chronology of memory consolidation: a review of functional inactivation findings. Neurobiol Learn Mem. 1999 Jan;71(1):1-18. doi: 10.1006/nlme.1998.3865.
- Background: PubMed 12536210Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. doi: 10.1038/nn1003. No abstract available.
- Background: PubMed 10190336Babinski LM, Hartsough CS, Lambert NM. Childhood conduct problems, hyperactivity-impulsivity, and inattention as predictors of adult criminal activity. J Child Psychol Psychiatry. 1999 Mar;40(3):347-55.
- Derived from this study: PubMed 30682530Hwang S, Meffert H, Parsley I, Tyler PM, Erway AK, Botkin ML, Pope K, Blair RJR. Segregating sustained attention from response inhibition in ADHD: An fMRI study. Neuroimage Clin. 2019;21:101677. doi: 10.1016/j.nicl.2019.101677. Epub 2019 Jan 15.
- Derived from this study: PubMed 29432037Tyler PM, White SF, Thompson RW, Blair RJR. Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools. Dev Neuropsychol. 2019 Jan-Feb;44(1):17-42. doi: 10.1080/87565641.2017.1334782. Epub 2018 Feb 12.
- Derived from this study: PubMed 28776147White SF, Thornton LC, Leshin J, Clanton R, Sinclair S, Coker-Appiah D, Meffert H, Hwang S, Blair JR. Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders. J Abnorm Child Psychol. 2018 May;46(4):741-754. doi: 10.1007/s10802-017-0335-0.
- Derived from this study: PubMed 26441155White SF, VanTieghem M, Brislin SJ, Sypher I, Sinclair S, Pine DS, Hwang S, Blair RJ. Neural Correlates of the Propensity for Retaliatory Behavior in Youths With Disruptive Behavior Disorders. Am J Psychiatry. 2016 Mar 1;173(3):282-90. doi: 10.1176/appi.ajp.2015.15020250. Epub 2015 Oct 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James J Blair, Ph.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Attention Deficit Disorder With Hyperactivity and Mental Disorders Diagnosed in Childhood, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00104039, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2019.