Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
Jeffrey Newcorn, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01678209
First received: August 30, 2012
Last updated: March 14, 2013
Last verified: March 2013
  Purpose

The growing number of medications used to treat attention-deficit/hyperactivity disorder (ADHD) raises important questions about whether different medications have similar or different therapeutic mechanisms of action. We have recently shown that the stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) produce clinical improvement via a common mechanism in motor cortex, and distinct actions in frontostriatal and midline cingulate-precuneus regions. These exciting findings offer a window into the common and unique neurophysiological mechanisms of response to stimulant and non-stimulant treatments. However, the interpretation and clinical utility of these results would be greatly enhanced by in-depth investigation of the impact of the two treatments on relevant neural networks, and analyses which evaluate whether improvement is achieved via normalization or other adaptive changes in brain function.


Condition Intervention Phase
Attention Deficit Hyperactivity Disorder
ADHD
Other: fMRI scans
Drug: Atomoxetine arm
Drug: Methylphenidate arm
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Brain Activation [ Time Frame: Baseline and at 6 - 8 weeks ] [ Designated as safety issue: No ]

    Comparison of brain activation at 6-8 weeks changed from baseline.

    a) 'Task-positive' regions; b) 'Task-negative' regions; c) 'Task-positive' regions and 'task-negative' regions;d) Normalization of reduced connectivity; e) Compensatory increases in functional connectivity



Secondary Outcome Measures:
  • Go-Nogo [ Time Frame: Baseline and at 6-8 weeks ] [ Designated as safety issue: No ]
    Comparison of Go-Nogo at 6-8 weeks changed from baseline. Performance on a go-nogo task inside the scanner

  • ADHD-RS [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    behavioral symptoms of ADHD


Estimated Enrollment: 144
Study Start Date: October 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: fMRI scans
Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
Other: fMRI scans
Control Group: will receive initial evaluation, and 2 fMRI scans each 6-8 weeks apart
Experimental: Atomoxetine arm
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan.
Drug: Atomoxetine arm
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks, and fMRI postscan.
Other Names:
  • Strattera
  • ATX
Experimental: Methylphenidate arm
subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
Drug: Methylphenidate arm
Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate for 6-8 weeks, and fMRI scan post treatment.
Other Names:
  • Concerta
  • MPH

Detailed Description:

The specific aims of this project are to use functional magnetic resonance imaging (fMRI) to determine the significance of activation changes over treatment related to clinical improvement, and the impact of treatment on neural connectivity within and between the anti-correlated frontostriatal 'task-positive' circuit and cingulate-precuneus 'task-negative' network. Our central hypotheses are that clinical improvement is associated with: (i) normalization of reduced connectivity of regions within the 'task-positive' network, with resultant increased inhibition of motor cortex, and (ii) normalization of low task-related connectivity in regions within the task-negative network for MPH and the 'task-positive' network for ATX.

This research proposes to test a model which posits a neurophysiological basis of mechanisms of response to stimulant and non-stimulant medications, and fits with our long term objectives of being able to match treatments to individual patients. Testing this model requires large samples of youth scanned using fMRI before and after treatment, and matched healthy controls also scanned twice. We will use an innovative network-based approach to study the effects of treatment, building on results from our current fMRI treatment study, and incorporating new theoretical approaches to understanding ADHD and its treatment.

  Eligibility

Ages Eligible for Study:   7 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

General inclusion criteria for subjects with ADHD and healthy controls are:

  • aged 7-17 years;
  • Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;
  • informed consent and assent to study participation.

Specific inclusion criteria for youth with ADHD are:

  • diagnosis of ADHD, any subtype, determined by Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Versions (K-SADS-PL);
  • ADHD Rating Scale-IV-Parent Version: Investigator Administered (ADHD-RSIV) total score ≥ 1.5 SD above age and gender means for subtype
  • Clinical Global Impressions-ADHD-Severity (CGI-S) score > 4;
  • ADHD must be the primary diagnosis and focus of treatment, and the treatments offered in the study must not be contraindicated for the comorbid disorder.

Exclusion Criteria:

General exclusion criteria are:

  • history of head injury with loss of consciousness or any CNS disease that is likely to affect brain function;
  • diagnosis of autism or pervasive developmental, psychotic, major mood, and Tourette's disorder;
  • alcohol or drug abuse in the past 3 months or a positive urinary toxic screen on initial evaluation;
  • use of psychotropic medication within 2 weeks of the study (8 weeks for fluoxetine);
  • pre-existing medical or psychological condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity);
  • metal in the body that precludes scanning (e.g., braces, metal plate);
  • positive urine pregnancy test.

Specific exclusion criteria for the treatment trial include:

  • previous unsuccessful trial of MPH or ATX that was adequately dosed (≥ 1 mg/kg for MPH or 1.0 mg/kg for ATX) and of adequate duration (≥ 4 weeks);
  • abnormal findings on physical exam, or vital signs
  • pulse and blood pressure > 95% of age and gender mean;
  • inability to swallow capsules;
  • weight is < 20 kg or > 85 kg.

Specific exclusion criteria for control youth include:

  • no past history or current diagnosis of any psychiatric disorder, determined by the K-SADS-PL interview;
  • ADHD-RS-IV and CBCL scores for each symptom domain ≤ 1 SD of age and gender means.
  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: NCT01678209

Contacts
Contact: Beth Krone, Doctoral Candidate 212-241-8012 Beth.Krone@mssm.edu
Contact: Jeffrey Newcorn, MD 212 659-8775 Jeffrey.Newcorn@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: Jeffrey Newcorn, MD         
Principal Investigator: Kurt Schulz, PhD         
Sponsors and Collaborators
Mount Sinai School of Medicine
Investigators
Principal Investigator: Jeffrey Newcorn, MD Mount Sinai School of Medicine
Principal Investigator: Kurt Schulz, PhD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Jeffrey Newcorn, Director Division of Child and Adolescent Psychiatry, Associate Professor Psychiatry and Pediatrics, Medical Director Center for Excellence for ADHD and Related Disorders, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01678209     History of Changes
Other Study ID Numbers: GCO 11-0161
Study First Received: August 30, 2012
Last Updated: March 14, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
Attention Deficit Hyperactivity Disorder
Stimulant
Non-stimulant
Drug
Methylphenidate
Atomoxetine
Strattera
Concerta
MACRO
Medication
Treatment
Youth
Adolescent
Functional Magnetic Resonance Imaging
Brain scan
Imaging
Response inhibition
Inattentive
Hyperactive
Combined
Medication Treatment
Brain Imaging

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
Central Nervous System Stimulants
Methylphenidate
Atomoxetine
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Adrenergic Uptake Inhibitors
Adrenergic Agents

ClinicalTrials.gov processed this record on October 19, 2014