Attention Deficit Hyperactivity DisorderPhase 4NERFNCT02478788
Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
A Phase 4 study testing mixed amphetamine salts-extended release (MAS-XR) in people with Attention Deficit Hyperactivity Disorder, run by University of Cincinnati at 1 site in United States.
Trial summary
The main purpose of this study is to see the affects of the study medication called mixed amphetamine salts-extended release (MAS-XR) on brain function by taking brain pictures. The researchers also want to see if MAS-XR makes your child more or less likely to develop problems like acting out (i.e. Read more about this study
- Who is it for?
- Ages 10 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- mixed amphetamine salts-extended release (MAS-XR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 153 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Dec 2022
- 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 10 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Ages 10-18years old
- If female, not pregnant
- Fluent in English
- No contraindication to an MRI scan (e.g., braces or claustrophobia)
- An IQ > 80
- No unstable or major medical or neurological illness
Show all 22Show fewer
- No lifetime DSM-5 substance use disorder
- Lives <100 miles from the University of Cincinnati
- Provision of written informed consent/assent
- At least one biological first degree relative with bipolar I disorder ('high-risk' only)
- No first- or second-degree relative with a mood or psychotic disorder ('low-risk' and healthy controls only) with the exception of late onset depressive disorders.
- No lifetime DSM-5 Axis I disorder (other than specific phobias, healthy controls only).
- No medications with CNS effects within 5 half-lives from baseline MR scan (healthy controls only).
- Inclusion criteria for 'high-risk' and 'low-risk' ADHD subjects :
- Meets DSM-5 criteria for ADHD, inattentive, hyperactive/impulsive, or combined type
- No exposure to psychostimulants or ADHD medications in the 3 months prior to baseline
- No lifetime exposure to mood stabilizers or antipsychotic medications
- No concomitant use of any psychotropic medication other than study medications during study participation
- No history of intolerance, hypersensitivity, or non-response to MAS-XR
- No comorbid mood, anxiety, conduct, eating or psychotic disorder that in the opinion of the primary investigator is the current and primary focus of treatment. No Tourette's disorder, chronic tic disorder, or autism spectrum disorder.
- No clinically significant ECG or blood pressure abnormalities
- No family history of sudden death or ventricular arrhythmia
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
Cincinnati, Ohio, 45219
About this study
The main purpose of this study is to see the affects of the study medication called mixed amphetamine salts-extended release (MAS-XR) on brain function by taking brain pictures. The researchers also want to see if MAS-XR makes your child more or less likely to develop problems like acting out (i.e. periods of irritability, agitation, aggression).
MAS-XR is approved by the United States Food and Drug Administration (FDA) to treat attention deficit hyperactivity disorder (ADHD) in adults, children and adolescents.
Read the detailed description
A 12-week prospective study of two groups of adolescents (ages 10-18 years) with attention deficit/hyperactivity disorder (ADHD); 1) ADHD adolescents with a first degree relative with bipolar disorder ("high-risk") and 2) ADHD adolescents without any first or second degree-relatives with a mood disorder ("low-risk"). Patients will be evaluated using diagnostic interviews and symptom ratings, will receive neuroimaging scans (fMRI, DTI, 1H MRS), and will then be assigned to treatment. Low-risk ADHD adolescents (n=60) will receive treatment with open-label mixed amphetamine salts-extended release (MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). Following initiation of treatment, the ADHD adolescents will have regularly scheduled visits during which symptom and tolerability ratings will be performed. Healthy subjects (n=60) will be recruited from the community and will not receive medication but will undergo magnetic resonance imaging (MRI) scans at the same intervals to assess normal variability in imaging parameters between time points as well as to adjust and interpret comparisons within patients (i.e., whether patient values are changing toward or away from those of healthy adolescents). Neuroimaging (fMRI, DTI,1H MRS) evaluations will be performed at baseline and Week 12 (or termination).
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- mixed amphetamine salts-extended release (MAS-XR), Placebo
- Keywords
- ADHD
- 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.
mixed amphetamine salts-extended release (MAS-XR)Drug
Also called AdderallXR
MAS-XR is a psychostimulant medication composed of amphetamine and dextroamphetamine, has been systematically studied in adolescents with ADHD, and is FDA-approved for the treatment of ADHD in adolescents.
PlaceboDrug
Pills with no medication in it
| Study group | Role | What they receive |
|---|---|---|
| LR-MAS - Low-risk ADHD adolescents | Experimental | ADHD adolescents without any first or second degree-relatives with bipolar disorder. Low-risk ADHD adolescents (n=60) will receive treatment with open-label mixed amphetamine salts-extended release (MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. Receives: Drug: mixed amphetamine salts-extended release (MAS-XR) |
| HR-MAS - High-risk ADHD adolescents | Experimental | ADHD adolescents with a parent with bipolar disorder ("high-risk"). High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). The subjects in this group will receive mixed amphetamine salts-extended release( MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. Receives: Drug: mixed amphetamine salts-extended release (MAS-XR) |
| HR-P - High-risk ADHD on Placebo | Placebo comparator | ADHD adolescents with a parent with bipolar disorder ("high-risk"). High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). Following initiation of treatment, the ADHD adolescents will have regularly scheduled visits during which symptom and tolerability ratings will be performed. Receives: Drug: Placebo |
| HC (Healthy Controls) | No intervention | Healthy subjects (n=60) will be recruited from the community and will not receive medication but will undergo MR scans at the same intervals to assess normal variability in imaging parameters between time points as well as to adjust and interpret comparisons within patients (i.e., whether patient values are changing toward or away from those of healthy adolescents). Neuroimaging evaluations will be performed at baseline and Week 12 (or termination). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Baseline-endpoint change in prefrontal-amygdala functional connectivity by fMRI.
Using functional magnetic resonance imaging (fMRI), change in prefrontal-amygdala functional connectivity will be determined by contrasting baseline and endpoint blood oxygen level-dependent (BOLD) activity in the amygdala and prefrontal cortex (BA47) during performance of the CPT-END task, and determining the prefrontal-amygdala interrelationship using a seed-region (amygdala) based functional connectivity analysis.
Measured: Baseline and up to 12 weeks
Secondary outcomes (2)
Baseline-endpoint change in uncinate fasciculus white matter integrity by DTI
Change in uncinate fasciculus white matter integrity will be determined by contrasting baseline and endpoint fractional anisotropy using diffusion tensor imaging (DTI).
Measured: Baseline and up to 12 weeks
Baseline-endpoint change in glutamate (Glu) and N-acetyl aspartate (NAA) concentrations in the prefrontal cortex (BA47) by 1H MRS.
This is a composite measure of change in right and left prefrontal cortex (BA47) Glu and NAA concentrations (mM). It will be determined by contrasting baseline and endpoint levels using proton magnetic resonance spectroscopy (1H MRS).
Measured: Baseline and up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study startNov 2015
- Primary completionAug 2022
- Study completionDec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Melissa Delbello, University of Cincinnati
- Investigators
- Robert McNamara, PhD, Study director, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02478788
- Sponsor's protocol ID
- DelBello/McNamara Neuroimaging
- Other IDs
- R01MH097818-01A1
- Acronym
- NERF
- Status last verified
- Sep 2023
- First submitted
- 15 Jun 2015
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tang B, Patino LR, Zhang W, Lui S, DelBello MP, McNamara RK. Regional cerebellar structural deficits distinguish psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder: a cross-sectional morphometric analysis. J Child Psychol Psychiatry. 2026 May;67(5):766-776. doi: 10.1111/jcpp.70072. Epub 2025 Nov 2.
PubMed 41177538Qin K, Pan N, Lei D, Zhu Z, Tallman MJ, Patino LR, Gong Q, Sweeney JA, DelBello MP, McNamara RK. Different Changes in Brain Functional Networks Following 12-Week Psychostimulant Treatment in Attention-Deficit/Hyperactivity Disorder Youth With and Without Familial Risk for Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry. 2026 Jul;65(7):917-928. doi: 10.1016/j.jaac.2025.07.421. Epub 2025 Jul 23.
PubMed 40712681Patino LR, Wilson AS, Tallman MJ, Blom TJ, DelBello MP, McNamara RK. Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder. J Atten Disord. 2024 Mar;28(5):820-833. doi: 10.1177/10870547231215292. Epub 2023 Dec 28.
PubMed 38153098
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
- ClinicalTrials.gov ID
- NCT02478788
- Acronym / sponsor ID
- NERF / DelBello/McNamara Neuroimaging
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- ADHD
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 2015 (actual)
- Primary completion
- Aug 2022 (actual)
- Study completion
- Dec 2022 (actual)
- First posted
- 23 Jun 2015 (estimated)
- 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 main purpose of this study is to see the affects of the study medication called mixed amphetamine salts-extended release (MAS-XR) on brain function by taking brain pictures. The researchers also want to see if MAS-XR makes your child more or less likely to develop problems like acting out (i.e. periods of irritability, agitation, aggression).
MAS-XR is approved by the United States Food and Drug Administration (FDA) to treat attention deficit hyperactivity disorder (ADHD) in adults, children and adolescents.
Detailed description
A 12-week prospective study of two groups of adolescents (ages 10-18 years) with attention deficit/hyperactivity disorder (ADHD); 1) ADHD adolescents with a first degree relative with bipolar disorder ("high-risk") and 2) ADHD adolescents without any first or second degree-relatives with a mood disorder ("low-risk"). Patients will be evaluated using diagnostic interviews and symptom ratings, will receive neuroimaging scans (fMRI, DTI, 1H MRS), and will then be assigned to treatment. Low-risk ADHD adolescents (n=60) will receive treatment with open-label mixed amphetamine salts-extended release (MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). Following initiation of treatment, the ADHD adolescents will have regularly scheduled visits during which symptom and tolerability ratings will be performed. Healthy subjects (n=60) will be recruited from the community and will not receive medication but will undergo magnetic resonance imaging (MRI) scans at the same intervals to assess normal variability in imaging parameters between time points as well as to adjust and interpret comparisons within patients (i.e., whether patient values are changing toward or away from those of healthy adolescents). Neuroimaging (fMRI, DTI,1H MRS) evaluations will be performed at baseline and Week 12 (or termination).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| LR-MAS - Low-risk ADHD adolescents | Experimental | Drug: mixed amphetamine salts-extended release (MAS-XR)ADHD adolescents without any first or second degree-relatives with bipolar disorder. Low-risk ADHD adolescents (n=60) will receive treatment with open-label mixed amphetamine salts-extended release (MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. |
| HR-MAS - High-risk ADHD adolescents | Experimental | Drug: mixed amphetamine salts-extended release (MAS-XR)ADHD adolescents with a parent with bipolar disorder ("high-risk"). High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). The subjects in this group will receive mixed amphetamine salts-extended release( MAS-XR), which is approved by the United States Food and Drug Administration (USFDA) for the treatment of ADHD and is a commonly prescribed psychostimulant medication for adolescents with ADHD. |
| HR-P - High-risk ADHD on Placebo | Placebo comparator | Drug: PlaceboADHD adolescents with a parent with bipolar disorder ("high-risk"). High-risk ADHD adolescents will be randomized to double-blind treatment with MAS-XR (n=60) or placebo (n=60). Following initiation of treatment, the ADHD adolescents will have regularly scheduled visits during which symptom and tolerability ratings will be performed. |
| HC (Healthy Controls) | No intervention | –Healthy subjects (n=60) will be recruited from the community and will not receive medication but will undergo MR scans at the same intervals to assess normal variability in imaging parameters between time points as well as to adjust and interpret comparisons within patients (i.e., whether patient values are changing toward or away from those of healthy adolescents). Neuroimaging evaluations will be performed at baseline and Week 12 (or termination). |
Who may qualify
- Ages
- 10 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- Ages 10-18years old
- If female, not pregnant
- Fluent in English
- No contraindication to an MRI scan (e.g., braces or claustrophobia)
- An IQ > 80
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| mixed amphetamine salts-extended release (MAS-XR)Also: AdderallXRMAS-XR is a psychostimulant medication composed of amphetamine and dextroamphetamine, has been systematically studied in adolescents with ADHD, and is FDA-approved for the treatment of ADHD in adolescents. | Drug | HR-MAS - High-risk ADHD adolescents, LR-MAS - Low-risk ADHD adolescents |
| PlaceboPills with no medication in it | Drug | HR-P - High-risk ADHD on Placebo |
Primary outcome
Baseline-endpoint change in prefrontal-amygdala functional connectivity by fMRI.
Time frame: Baseline and up to 12 weeks
Using functional magnetic resonance imaging (fMRI), change in prefrontal-amygdala functional connectivity will be determined by contrasting baseline and endpoint blood oxygen level-dependent (BOLD) activity in the amygdala and prefrontal cortex (BA47) during performance of the CPT-END task, and determining the prefrontal-amygdala interrelationship using a seed-region (amygdala) based functional connectivity analysis.
2 secondary outcomes
Baseline-endpoint change in uncinate fasciculus white matter integrity by DTI
Time frame: Baseline and up to 12 weeks
Baseline-endpoint change in glutamate (Glu) and N-acetyl aspartate (NAA) concentrations in the prefrontal cortex (BA47) by 1H MRS.
Time frame: Baseline and up to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
- Derived from this study: PubMed 41177538Tang B, Patino LR, Zhang W, Lui S, DelBello MP, McNamara RK. Regional cerebellar structural deficits distinguish psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder: a cross-sectional morphometric analysis. J Child Psychol Psychiatry. 2026 May;67(5):766-776. doi: 10.1111/jcpp.70072. Epub 2025 Nov 2.
- Derived from this study: PubMed 40712681Qin K, Pan N, Lei D, Zhu Z, Tallman MJ, Patino LR, Gong Q, Sweeney JA, DelBello MP, McNamara RK. Different Changes in Brain Functional Networks Following 12-Week Psychostimulant Treatment in Attention-Deficit/Hyperactivity Disorder Youth With and Without Familial Risk for Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry. 2026 Jul;65(7):917-928. doi: 10.1016/j.jaac.2025.07.421. Epub 2025 Jul 23.
- Derived from this study: PubMed 38153098Patino LR, Wilson AS, Tallman MJ, Blom TJ, DelBello MP, McNamara RK. Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder. J Atten Disord. 2024 Mar;28(5):820-833. doi: 10.1177/10870547231215292. Epub 2023 Dec 28.
Related trials for Attention Deficit Hyperactivity Disorder
Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
ADHD
Not yet recruitingPhase 2
Lisdexamfetamine For the Treatment of Conduct Disorder in Children
Conduct Disorder
RecruitingObservational study
Augmenting Parent Management Training for Child Temper Outbursts Using a Digital Tool
Disruptive Behavior Disorders, Conduct Disorder
Recruiting
Micronutrient Supplementation and Chronotherapy in Children With ADHD
Attention Deficit Hyperactivity Disorder (ADHD)
RecruitingPhase 3
Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol (FOCUS-2)
ADHD
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.
Robert McNamara, PhD study director
University of Cincinnati
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 mixed amphetamine salts-extended release (MAS-XR) in people with Attention Deficit Hyperactivity Disorder, run by University of Cincinnati 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 22 inclusion and 0 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 21 Sep 2023. 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Baseline-endpoint change in prefrontal-amygdala functional connectivity by fMRI. (time frame: Baseline and up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02478788, which also lists 3 linked publications.
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 21 Sep 2023.