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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Floyd Sallee, University of Cincinnati
ClinicalTrials.gov Identifier:
NCT01330693
First received: April 5, 2011
Last updated: December 27, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Attention Deficit Disorder With Hyperactivity
Drug: Atomoxetine
Drug: Sugar Pill
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Cortical Excitability: Phenotype and Biomarker in ADHD Therapy

Resource links provided by NLM:


Further study details as provided by University of Cincinnati:

Primary Outcome Measures:
  • Efficacy outcome as change from baseline in ADHDRS total score [ Time Frame: At 4 weeks ] [ Designated as safety issue: No ]
  • SICI as a marker of ADHD Behaviors [ Time Frame: Baseline visit ] [ Designated as safety issue: No ]
    To evaluate pTMS-evoked Short Interval Cortical Inhibition (SICI) as a marker of the hyperactive-impulsive dimension in Attention Deficit Hyperactivity Disorder

  • Cognitive Correlates of SICI Change [ Time Frame: 2 hours (at baseline visit) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 120
Study Start Date: September 2009
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Sugar Pill

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.

  Eligibility

Ages Eligible for Study:   7 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01330693

Locations
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
Investigators
Principal Investigator: Floyd R Sallee, MD University of Cincinnati
  More Information

No publications provided

Responsible Party: Floyd Sallee, Professor, University of Cincinnati
ClinicalTrials.gov Identifier: NCT01330693     History of Changes
Other Study ID Numbers: 1R01MH081854-01A2, 1R01MH081854-01A2
Study First Received: April 5, 2011
Last Updated: December 27, 2013
Health Authority: United States: National Children's Hospital, Washington, DC.
United States: Institutional Review Board

Keywords provided by University of Cincinnati:
ADHD
Atomoxetine
Biomarker

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Hyperkinesis
Attention Deficit and Disruptive Behavior Disorders
Mental Disorders Diagnosed in Childhood
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Contraceptives, Oral
Atomoxetine
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014