Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 5R01MH095766-02 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| fMRI scans | Active Comparator | Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart |
|
| Atomoxetine arm | Experimental | 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. |
|
| Methylphenidate arm | Experimental | Subjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fMRI scans | Other | 2 fMRI scans 6-8 weeks apart |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline and at 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
| Clinical Global Impressions-Severity (CGI-S) |
Not provided
Inclusion Criteria:
General inclusion criteria for subjects with ADHD and healthy controls are:
Specific inclusion criteria for youth with ADHD are:
Exclusion Criteria:
General exclusion criteria are:
Specific exclusion criteria for the treatment trial include:
Specific exclusion criteria for control youth include:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Newcorn, MD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Kurt Schulz, PhD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
Not provided
Recruitment: 8/10/2012 - 4/30/17; Roll Over Year: 5/1/17 - 4/30/18; Youth with ADHD and Healthy Controls recruited from the community and clinics at Mount Sinai.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Control Group fMRI Scans Only | Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart |
| FG001 | Atomoxetine Arm | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Only participants with usable data were included in the data results
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Control Group fMRI Scans Only | Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart |
| BG001 | Atomoxetine Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. Thirty-one (N=31) controls were scanned twice for this project, but the second scan data for 1 subject was excluded from the analysis for motion. Thus, 31 control subjects were included in the analyses of | Posted | Mean | Standard Deviation | percent correct inhibition | Baseline and at 6 weeks |
|
8 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | fMRI Scans | Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Decreased appetite | Gastrointestinal disorders | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Beth Krone, PhD | Icahn School of Medicine at Mount Sinai | 212-241-8014 | beth.krone@mssm.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 6, 2019 | May 13, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2019 | May 22, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| D013035 | Spasm |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
| D020879 | Neuromuscular Manifestations |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069445 | Atomoxetine Hydrochloride |
| D008774 | Methylphenidate |
| C041626 | 5,10-dihydro-5-methylphenazine |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D010648 | Phenylacetates |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Atomoxetine arm | Drug | Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks |
|
|
| Methylphenidate arm | Drug | Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits. |
|
|
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. |
| up to 6 weeks |
| 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. | baseline and at 6 weeks |
| 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. | baseline and at 6 weeks |
| 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. | baseline and at 6 weeks |
| 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. | baseline and at 6 weeks |
| screen fail |
|
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.
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Atomoxetine Arm | 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. |
| OG002 | 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. |
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis. | Posted | Mean | Standard Deviation | score on a scale | 8 weeks |
|
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis. | Posted | Mean | Standard Deviation | score on a scale | up to 6 weeks |
|
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. | Posted | Mean | Standard Deviation | milliseconds | baseline and at 6 weeks |
|
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. | Posted | Mean | Standard Deviation | commissioned t-score | baseline and at 6 weeks |
|
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. | Posted | Mean | Standard Deviation | score on a scale | baseline and at 6 weeks |
|
|
|
| Secondary | 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. | All participants in control group including the one subject who could not be scanned twice included in data analysis for the 6 weeks visit. | Posted | Mean | Standard Deviation | score on a scale | baseline and at 6 weeks |
|
|
|
| 0 |
| 47 |
| 0 |
| 47 |
| 3 |
| 47 |
| EG001 | Atomoxetine Arm | 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. | 0 | 22 | 0 | 22 | 6 | 22 |
| EG002 | 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. | 0 | 22 | 0 | 22 | 4 | 22 |
| Stomachache | Gastrointestinal disorders | Non-systematic Assessment |
|
| Headache | General disorders | Non-systematic Assessment |
|
| Moody/irritable | Psychiatric disorders | Non-systematic Assessment |
|
| Common cold/allergies | General disorders | Non-systematic Assessment |
|
| Anxious | Psychiatric disorders | Non-systematic Assessment |
|
| Sleep problems | General disorders | Non-systematic Assessment |
|
| Lightheaded/dizzy | General disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Increased blood pressure | Vascular disorders | Non-systematic Assessment |
|
Dr. Newcorn has FCOI reporting obligations as stipulated by the Mount Sinai FCOI committee
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000146 |
| Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| 6 weeks |
|
|
| 6 weeks |
|
|
| 6 weeks |
|
|
| 6 weeks |
|
|