Attention Deficit Hyperactivity DisorderPhase 4NCT01678209
Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
A Phase 4 study testing fMRI scans, Atomoxetine arm and Methylphenidate arm in people with Attention Deficit Hyperactivity Disorder and ADHD, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 7 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder, ADHD
- What is being tested?
- fMRI scans, Atomoxetine arm and Methylphenidate arm
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to 30 Apr 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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);
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- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
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.
Read the 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.
- Conditions
- Attention Deficit Hyperactivity Disorder, ADHD
- Being tested
- fMRI scans, Atomoxetine arm, Methylphenidate arm
- 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
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity, Spasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fMRI scansOther
2 fMRI scans 6-8 weeks apart
Atomoxetine armDrug
Also called Strattera, ATX
Flexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks
Methylphenidate armDrug
Also called Concerta, MPH
Flexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits.
| Study group | Role | What they receive |
|---|---|---|
| fMRI scans | Active comparator | Healthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart Receives: Other: fMRI scans |
| 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. Receives: Other: fMRI scans; Drug: Atomoxetine arm |
| 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. Receives: Other: fMRI scans; Drug: Methylphenidate arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and at 6 weeks
Secondary outcomes (6)
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.
Measured: 8 weeks
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline and at 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2012 (estimated)
- Study startOct 2012
- Primary completion30 Apr 2018
- Study completion30 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Jeffrey Newcorn, Icahn School of Medicine at Mount Sinai
- Investigators
- Jeffrey Newcorn, MD, Principal investigator, Icahn School of Medicine at Mount SinaiKurt Schulz, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01678209
- Sponsor's protocol ID
- GCO 11-0161
- Other IDs
- 5R01MH095766-02
- Status last verified
- Jul 2020
- First submitted
- 30 Aug 2012
- Last updated
- 24 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging Stimulant and Non Stimulant Treatments for ADHD: A Network Based Approach
- ClinicalTrials.gov ID
- NCT01678209
- Acronym / sponsor ID
- GCO 11-0161
- Conditions
- Attention Deficit Hyperactivity Disorder, ADHD
- Keywords
- Attention Deficit Hyperactivity Disorder, Stimulant, Non-stimulant, Drug, Methylphenidate, Atomoxetine, Strattera, Concerta
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2012
- Primary completion
- 30 Apr 2018 (actual)
- Study completion
- 30 Apr 2018 (actual)
- First posted
- 3 Sep 2012 (estimated)
- Results
- Posted 24 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| fMRI scans | Active comparator | Other: fMRI scansHealthy Control Group: will receive initial evaluation, and 2 fMRI (functional magnetic resonance imaging) scans each 6-8 weeks apart |
| Atomoxetine arm | Experimental | Other: fMRI scans, Drug: Atomoxetine armThese 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 | Other: fMRI scans, Drug: Methylphenidate armSubjects will receive initial evaluation, baseline fMRI scan, flexible dose titration with methylphenidate (Concerta) for 6-8 weeks, and fMRI scan post treatment. |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- aged 7-17 years;
- Wechsler Intelligence Scale for Children (WISC) scores ≥ 75;
- informed consent and assent to study participation.
- 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
Key exclusion criteria (17 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fMRI scans2 fMRI scans 6-8 weeks apart | Other | Atomoxetine arm, Methylphenidate arm, fMRI scans |
| Atomoxetine armAlso: Strattera, ATXFlexible dose titration with atomoxetine prescribed at weekly visits for 6-8 weeks | Drug | Atomoxetine arm |
| Methylphenidate armAlso: Concerta, MPHFlexible dose titration with methylphenidate for 6-8 weeks, with optional post study stabilization visits. | Drug | Methylphenidate arm |
Primary outcome
Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task
Time frame: Baseline and at 6 weeks
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).
6 secondary outcomes
Adult Attention Deficit Hyperactivity Disorder Investigator Symptom Rating Scale (ADHD-RS)
Time frame: 8 weeks
Clinical Global Impressions-Severity (CGI-S)
Time frame: up to 6 weeks
Response Time in Attention Networks Test (ANT)
Time frame: baseline and at 6 weeks
Continuous Performance Test (CPT)
Time frame: baseline and at 6 weeks
Digit Span
Time frame: baseline and at 6 weeks
Finger Windows
Time frame: baseline and at 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Newcorn, MD principal investigator
Icahn School of Medicine at Mount Sinai
Kurt Schulz, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing fMRI scans, Atomoxetine arm and Methylphenidate arm in people with Attention Deficit Hyperactivity Disorder and ADHD, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Correct Inhibition in Participants Assessed With the Go-No go Task (time frame: Baseline and at 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2020.