ADHDPhase 4MPH-ATXNCT03781765
Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk
A Phase 4 study testing Methylphenidate and Atomoxetine in people with ADHD and Attention Deficit Hyperactivity Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The study team will examine the effects of FDA approved stimulant and non-stimulant medications for ADHD, among youth with ADHD and with and without Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD), on reward systems of the brain using fMRI. Read more about this study
- Who is it for?
- Ages 7 to 12 years
- Conditions the study is for
- ADHD, Attention Deficit Hyperactivity Disorder
- What is being tested?
- Methylphenidate and Atomoxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Jun 2019to 25 Sep 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Pre-pubertal (e.g. Tanner stage 1 or 2)
- Age 7-12 inclusive
- Signed consent/assent
- Parent communicates sufficiently in English to provide informed consent and complete assessment instruments;
- ADHD as determined by computerized DISC (C-DISC) parent interview
- ADHD-Rating Scale-5 total score (interview with parent )
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- SNAP ADHD total score (teacher) of 1.5 SD > age/sex norms
- CD or severe ODD: CD or ODD + 2 symptoms of CD on C-DISC
- SNAP ODD/CD subscale (parent and teacher) 1.5 SD > age/sex norms
Who cannot join
- Major neurological/medical illness
- History of head injury
- Fetal exposure to alcohol/drugs
- Diagnosis of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, generalized anxiety, social phobia, Tourette's Disorder, PTSD, autism spectrum disorder)
- Current suicidal ideation or past history of suicide attempt
- Wechsler Abbreviated Scale of Intelligence (WASI)75 score <75
Show all 15Show fewer
- Prior or current treatment with stimulants (prior or current treatment with non-stimulants is permitted, but participants must be off medication for 2 weeks at baseline)
- Current or past alcohol/drug use (DISC interview; urine toxicology)
- Psychological or medical condition which precludes being in the scanner (e.g., claustrophobia, morbid obesity)
- Metal in the body that cannot be removed (e.g., braces, metal plate)
- Visual disturbances that may impair task performance
- Precocious puberty (e.g. Tanner stage >2) or pregnancy
- Notes:
- History of SUD in a 1st degree relative is permitted, and is expected in ~1/2 of the subjects
- Ongoing psychosocial treatment is allowed but should not be initiated during the study
Trial locations and contacts
1 site in 1 country.
Jeffrey Newcorn, MD contact
United States1 site, 1 recruiting
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Beth Krone, PhD, 212-241-8012, beth.krone@mssm.edu
Jeffrey Newcorn, MD
About this study
The study team will examine the effects of FDA approved stimulant and non-stimulant medications for ADHD, among youth with ADHD and with and without Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD), on reward systems of the brain using fMRI.
Read the detailed description
Longitudinal studies have shown that childhood Attention Deficit/Hyperactivity Disorder (ADHD) and child disruptive behavior disorders play an important role in the development of later Substance Use Disorders (SUD). Although available evidence suggests that abnormal reward processing is likely to mediate vulnerability for addiction, the functioning of the brain reward systems in at-risk individuals preceding the exposure to drugs remains largely unknown. Better understanding the baseline characteristics of reward processing in drug-naïve individuals at risk for later SUD is an important initial step in refining our knowledge of the neurobiological basis of addiction. Reward processing in at-risk individuals may be further influenced by exposure to first-line treatments (e.g. methylphenidate (MPH)) for ADHD that also happen to be controlled substances.
Findings from animal research have raised the possibility that stimulants such as methylphenidate (MPH) may have "sensitization" effects - which prime the brain reward system for enhanced responding to the rewarding effects of abusable substances, whereas non-stimulants such as atomoxetine (ATX) may diminish drug self-administration. However, no studies have examined the purported different effects of stimulants vs. non-stimulants on the brain reward system utilizing a targeted biomarker approach linked to an a priori model, which focuses on intermediate phenotypes. Such research could provide important knowledge regarding the biological basis of addiction vulnerability and aid in the development of preventive interventions.
This proposal will provide pilot data for the hypotheses that stimulant and non-stimulant medications have differential effects on activation in the brain reward system in High Risk (HR) youth, and that differences activation will be related to changes in measures of reward sensitivity on psychometric tests. The study team believes that this protocol is uniquely innovative in its approach to study drug-naïve children at the highest levels of risk for SUD, thus providing an opportunity to delineate differential effects of medication treatment in relation to SUD risk. This research is also significant since it will be the first neuroimaging study to assess the biological correlates of the effects of stimulants on reward sensitivity in HR children, and especially in relation to purported changes in reward processing.
- Conditions
- ADHD, Attention Deficit Hyperactivity Disorder
- Being tested
- Methylphenidate, Atomoxetine
- Keywords
- fMRI Study, MPH, Methylphenidate, ATX, Atomoxetine, Reward System, Substance Abuse Risk
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called MPH
stimulant medication
AtomoxetineDrug
Also called ATX
non-stimulant medication
| Study group | Role | What they receive |
|---|---|---|
| Methylphenidate | Active comparator | 0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks Receives: Drug: Methylphenidate |
| Atomoxetine | Active comparator | 0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks Receives: Drug: Atomoxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
fMRI Measure
Bold activation change within the reward system (e.g., ventral striatum, insula and orbitofrontal cortex)
Measured: 3 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start4 Jun 2019
- Primary completion25 Sep 2025 (estimated)
- Study completion25 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ADHDStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- This is a pilot study with no control group. All youth will be treated with MPH or ATX and receive pre and post fMRI.
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- 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 SinaiIliyan Ivanov, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03781765
- Sponsor's protocol ID
- GCO 17-0423
- Other IDs
- 1R21DA045218-01A1
- Acronym
- MPH-ATX
- Status last verified
- Aug 2024
- First submitted
- 18 Dec 2018
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stimulant vs. Non-stimulant Treatments and Reward Processing in Drug-naive Youth at SUD Risk
- ClinicalTrials.gov ID
- NCT03781765
- Acronym / sponsor ID
- MPH-ATX / GCO 17-0423
- Conditions
- ADHD, Attention Deficit Hyperactivity Disorder
- Keywords
- fMRI Study, MPH, Methylphenidate, ATX, Atomoxetine, Reward System, Substance Abuse Risk
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 4 Jun 2019 (actual)
- Primary completion
- 25 Sep 2025 (estimated)
- Study completion
- 25 Sep 2025 (estimated)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study team will examine the effects of FDA approved stimulant and non-stimulant medications for ADHD, among youth with ADHD and with and without Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD), on reward systems of the brain using fMRI.
Detailed description
Longitudinal studies have shown that childhood Attention Deficit/Hyperactivity Disorder (ADHD) and child disruptive behavior disorders play an important role in the development of later Substance Use Disorders (SUD). Although available evidence suggests that abnormal reward processing is likely to mediate vulnerability for addiction, the functioning of the brain reward systems in at-risk individuals preceding the exposure to drugs remains largely unknown. Better understanding the baseline characteristics of reward processing in drug-naïve individuals at risk for later SUD is an important initial step in refining our knowledge of the neurobiological basis of addiction. Reward processing in at-risk individuals may be further influenced by exposure to first-line treatments (e.g. methylphenidate (MPH)) for ADHD that also happen to be controlled substances.
Findings from animal research have raised the possibility that stimulants such as methylphenidate (MPH) may have "sensitization" effects - which prime the brain reward system for enhanced responding to the rewarding effects of abusable substances, whereas non-stimulants such as atomoxetine (ATX) may diminish drug self-administration. However, no studies have examined the purported different effects of stimulants vs. non-stimulants on the brain reward system utilizing a targeted biomarker approach linked to an a priori model, which focuses on intermediate phenotypes. Such research could provide important knowledge regarding the biological basis of addiction vulnerability and aid in the development of preventive interventions.
This proposal will provide pilot data for the hypotheses that stimulant and non-stimulant medications have differential effects on activation in the brain reward system in High Risk (HR) youth, and that differences activation will be related to changes in measures of reward sensitivity on psychometric tests. The study team believes that this protocol is uniquely innovative in its approach to study drug-naïve children at the highest levels of risk for SUD, thus providing an opportunity to delineate differential effects of medication treatment in relation to SUD risk. This research is also significant since it will be the first neuroimaging study to assess the biological correlates of the effects of stimulants on reward sensitivity in HR children, and especially in relation to purported changes in reward processing.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a pilot study with no control group. All youth will be treated with MPH or ATX and receive pre and post fMRI.
| Arm | Type | Receives |
|---|---|---|
| Methylphenidate | Active comparator | Drug: Methylphenidate0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks |
| Atomoxetine | Active comparator | Drug: Atomoxetine0.5 mg/kg for 1 week and 1 mg/kg for 2 weeks |
Who may qualify
- Ages
- 7 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Pre-pubertal (e.g. Tanner stage 1 or 2)
- Age 7-12 inclusive
- Signed consent/assent
- Parent communicates sufficiently in English to provide informed consent and complete assessment instruments;
- ADHD as determined by computerized DISC (C-DISC) parent interview
Key exclusion criteria (15 listed)
- Major neurological/medical illness
- History of head injury
- Fetal exposure to alcohol/drugs
- Diagnosis of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, generalized anxiety, social phobia, Tourette's Disorder, PTSD, autism spectrum disorder)
- Current suicidal ideation or past history of suicide attempt
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 |
|---|---|---|
| MethylphenidateAlso: MPHstimulant medication | Drug | Methylphenidate |
| AtomoxetineAlso: ATXnon-stimulant medication | Drug | Atomoxetine |
Primary outcome
fMRI Measure
Time frame: 3 Weeks
Bold activation change within the reward system (e.g., ventral striatum, insula and orbitofrontal cortex)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Individual participant dataSharing planned: No
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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 contact
Jeffrey Newcorn, MD principal investigator
Icahn School of Medicine at Mount Sinai
Iliyan Ivanov, MD 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 Methylphenidate and Atomoxetine in people with ADHD and Attention Deficit Hyperactivity Disorder, 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 15 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: status not confirmed, as of the sponsor's last update on 9 Aug 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Beth Krone, PhD (212-241-8012, beth.krone@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
fMRI Measure (time frame: 3 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 9 Aug 2024.