Back to resultsImaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
Primary Purpose
Attention Deficit Hyperactivity Disorder, ADHD
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
fMRI scans
Atomoxetine arm
Methylphenidate arm
Sponsored by
About this trial
This is an interventional treatment trial for Attention Deficit Hyperactivity Disorder focused on measuring 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
Eligibility 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.
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
fMRI scans
Atomoxetine arm
Methylphenidate arm
Arm Description
Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.
Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
Outcomes
Primary Outcome Measures
Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).
Secondary Outcome Measures
Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.
Clinical Global Impressions-Severity (CGI-S)
a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Response Time in Attention Networks Test (ANT)
A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.
Continuous Performance Test (CPT)
A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.
Digit Span
A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.
Finger Windows
A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.
Full Information
NCT ID
NCT01678209
First Posted
August 30, 2012
Last Updated
July 7, 2020
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT01678209
Brief Title
Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
Official Title
Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
April 30, 2018 (Actual)
Study Completion Date
April 30, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Hyperactivity Disorder, ADHD
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
127 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fMRI scans
Arm Type
Active Comparator
Arm Description
Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart
Arm Title
Atomoxetine arm
Arm Type
Experimental
Arm Description
These subjects will receive initial evaluation and baseline fMRI scan, flexible dose titration with atomoxetine for 6-8 weeks, and fMRI postscan, with optional post study stabilization visits.
Arm Title
Methylphenidate arm
Arm Type
Experimental
Arm Description
Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment.
Intervention Type
Other
Intervention Name(s)
fMRI scans
Intervention Description
2 fMRI scans 6-8 weeks apart
Intervention Type
Drug
Intervention Name(s)
Atomoxetine arm
Other Intervention Name(s)
Strattera, ATX
Intervention Description
Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks
Intervention Type
Drug
Intervention Name(s)
Methylphenidate arm
Other Intervention Name(s)
Concerta, MPH
Intervention Description
Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
Primary Outcome Measure Information:
Title
Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
Description
Comparison of Go-Nogo at 6 weeks from baseline. Performance on a go-nogo task inside the scanner (fMRI). In the go/no-go task, participants respond to certain stimuli ("go" stimuli) and make no response for others ("no-go" stimuli).
Time Frame
Baseline and at 6 weeks
Secondary Outcome Measure Information:
Title
Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
Description
ADHD-RS is an 18-item list of core ADHD symptoms, each item are scored on a 4-point scale from 0-3, with total 0-54, with higher score indicating more symptoms.
Time Frame
8 weeks
Title
Clinical Global Impressions-Severity (CGI-S)
Description
a clinician rated measure of symptom severity. CGI-S is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Time Frame
up to 6 weeks
Title
Response Time in Attention Networks Test (ANT)
Description
A neuropsychological assessment of attention compared at 6 weeks from baseline by looking at response time. The ANT is a task designed to test three attentional networks in children and adults: alerting, orienting, and executive control. The response time were summed.
Time Frame
baseline and at 6 weeks
Title
Continuous Performance Test (CPT)
Description
A neuropsychological assessment of attention compared at 6 weeks from baseline. CPT is a task-oriented computerized assessment of attention-related problems.This score indicates the number of times the client responded but no target was presented. A fast reaction time and high commission error rate points to difficulties with impulsivity. A slow reaction time with high commission and omission errors, indicates inattention in general. Scores are compared with the normative scores for the age, group and gender of the person being tested and represented as a commissioned T-score. The T-score indicates the degree to which performance in CPT task is higher or lower than the performance of a healthy individual matched in age. A T-score of 50 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more attention-related problems.
Time Frame
baseline and at 6 weeks
Title
Digit Span
Description
A cognitive/neuropsychological measure of auditory/verbal working memory compared at 6 weeks from baseline. Digit Span. Memory span is the longest list of items that a person can repeat back in correct order immediately after presentation on 50% of all trials. Items may include words, numbers, or letters. The task is known as digit span when numbers are used. Memory span is a common measure of short-term memory. A digit-span task is used to measure working memory's number storage capacity.The item score is the sum of the scores on the two trials for that item (range=0-2). The total raw score for backwards digit span is the sum of the item scores; maximum backwards digit span total raw score is 0-16 points. Higher score indicates better health outcomes.
Time Frame
baseline and at 6 weeks
Title
Finger Windows
Description
A neuropsychological measure of motor skill and visual-spatial working memory compared at 6 weeks from baseline. The Finger Windows subtest is a measure of nonverbal, rote sequential recall. scaled scores ranging from 1 to 19, with higher score indicating better attention or concentration.
Time Frame
baseline and at 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Newcorn, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kurt Schulz, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
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