Cortical Excitability: Phenotype and Biomarker in Attention-deficit, Hyperactivity Disorder (ADHD) Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01330693
Recruitment Status : Unknown
Verified August 2015 by Floyd Sallee, University of Cincinnati.
Recruitment status was:  Active, not recruiting
First Posted : April 7, 2011
Last Update Posted : August 19, 2015
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Floyd Sallee, University of Cincinnati

Brief Summary:
The purpose of this study is to find out if children with attention-deficit, hyperactivity disorder (ADHD) have a difference in how their brain cells "fire" or react. The investigators also want to find if brain cell "firing" can tell us how severe of symptoms a child has from ADHD. Finally, the investigators want to see if giving an ADHD medication called atomoxetine can make the ADHD symptoms in a child better and if the improvement shows a change in brain "firing".

Condition or disease Intervention/treatment Phase
Attention Deficit Disorder With Hyperactivity Drug: Atomoxetine Drug: Sugar Pill Phase 3

Detailed Description:
This study will evaluate Short Interval Intracortical Inhibition (SICI) measured by pTMS as a marker of the hyperactive-impulsive dimension in 120 ADHD 7-12 years, medication-free children. This study will characterize the effects of a single dose of atomoxetine compared to placebo on cognitive correlates of SICI change. Participants will be randomized 2:1 to either atomoxetine or placebo. The study will also characterize the effects of four weeks of atomoxetine treatment on cortical inhibition and will correlate SICI change with clinical outcomes.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Cortical Excitability: Phenotype and Biomarker in ADHD Therapy
Study Start Date : September 2009
Estimated Primary Completion Date : November 2015
Estimated Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Atomoxetine
Atomoxetine is FDA-approved for the treatment of ADHD symptoms in children
Drug: Atomoxetine
Atomoxetine is FDA-approved for the treatment of ADHD symptoms in children. Single dose of 0.5 mg/kg at baseline visit. Then dose adjusted in an open-label design afterwards.
Other Name: Strattera

Placebo Comparator: Placebo
Sugar pill
Drug: Sugar Pill
In-active sugar pill randomly assigned at baseline visit

Primary Outcome Measures :
  1. Efficacy outcome as change from baseline in ADHDRS total score [ Time Frame: At 4 weeks ]
  2. SICI as a marker of ADHD Behaviors [ Time Frame: Baseline visit ]
    To evaluate pTMS-evoked Short Interval Cortical Inhibition (SICI) as a marker of the hyperactive-impulsive dimension in Attention Deficit Hyperactivity Disorder

  3. Cognitive Correlates of SICI Change [ Time Frame: 2 hours (at baseline visit) ]
    To determine cognitive correlates of SICI change, the study will first measure SICI at at rest and concurrently during the Stop-task. This process will then be repeated 2 hours after a single dose (0.5 mg/kg) of atomoxetine (ATX) or placebo.

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Ages Eligible for Study:   7 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed informed consent and assent
  2. Meets DSM-IV criteria for ADHD, combined or inattentive subtype, based on K-SADS interview
  3. Scores at least 1.5 SD higher than age and gender mean on ADHD RS, keyed to ADHD subtype (i.e., combined score for the combined subtype, inattentive subscale only for inattentive subtype, etc.)
  4. Age: 7 - 12 years at study entry
  5. Findings on physical exam, laboratory studies and ECG are judged to be normal for age and gender, as determined by study physician at study entry
  6. There is not a co-existing medical condition for which TMS or ATX is contraindicated (for example pheochromocytoma).
  7. Pulse and blood pressure within 95% of age and gender mean
  8. Full scale IQ >75 (i.e., excluding mental retardation and the lower level of the borderline range)
  9. Able to complete study instruments and swallow capsules
  10. Willing to commit to the entire visit schedule for the study
  11. No previous treatment with Atomoxetine
  12. Must either be naive to ADHD study medication or not doing well on the current ADHD medication.

Exclusion Criteria:

  1. Has one of the following exclusionary diagnoses: autism/ pervasive developmental disorder, mental retardation, schizophrenia, a psychotic disorder, bipolar disorder, severe depressive or conduct disorder
  2. Has a comorbid disorder that is otherwise allowable, but which requires a treatment that is not being offered in the study, and should be the primary focus of treatment, in the opinion of the PI
  3. Has a medical or neurologic disorder that would preclude taking the ATX, or which would potentially confound the assessment of ADHD and/or TMS outcomes, in the opinion of the PI (for example pheochromocytoma, or for specific purposes of this study uncontrolled seizure disorder or organic brain syndrome).
  4. Taking a systemic medication which might interfere with the metabolism or efficacy assessment of ATX in this study
  5. History of allergic reactions to multiple medications
  6. History of alcohol or drug abuse in the past 3 months Has been in a medication treatment study in the past 30 days
  7. Females of childbearing age who are sexually active, do not use acceptable birth control (double barrier method), or are not abstinent. Abstinence is defined as no sexual activity for at least 3 months before the start of the study and the intention to abstain from sexual activity during the study period). Double barrier methods allowed include: condoms or diaphragms combined with spermicide use, intrauterine devices (IUD), and oral, transdermal, injectable or implantable hormonal medications (Ortho-Evra, Norplant, Depo-Provera, and similar prescription products) for at least one month before entering the study and continuing its use throughout the study. Birth control pills alone are not acceptable forms of birth control for this study.
  8. Has any prior neurological condition that might increase the risk of an adverse event with TMS. For the purpose of this study we are excluding children with a current or prior history of epilepsy.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01330693

United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
University of Cincinnati
National Institute of Mental Health (NIMH)
Principal Investigator: Floyd R Sallee, MD University of Cincinnati

Responsible Party: Floyd Sallee, Professor, University of Cincinnati Identifier: NCT01330693     History of Changes
Other Study ID Numbers: 1R01MH081854-01A2 ( U.S. NIH Grant/Contract )
1R01MH081854-01A2 ( U.S. NIH Grant/Contract )
First Posted: April 7, 2011    Key Record Dates
Last Update Posted: August 19, 2015
Last Verified: August 2015

Keywords provided by Floyd Sallee, University of Cincinnati:

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Mental Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Atomoxetine Hydrochloride
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs