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Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder (NERF)

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ClinicalTrials.gov Identifier: NCT02478788
Recruitment Status : Recruiting
First Posted : June 23, 2015
Last Update Posted : April 13, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Melissa Delbello, University of Cincinnati

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Attention Deficit Hyperactivity Disorder Drug: mixed amphetamine salts-extended release (MAS-XR) Drug: Placebo Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Other
Official Title: Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
Actual Study Start Date : November 2015
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder

Arm Intervention/treatment
Experimental: LR-MAS - Low-risk ADHD adolescents
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.
Drug: mixed amphetamine salts-extended release (MAS-XR)
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.
Other Name: AdderallXR

Experimental: HR-MAS - High-risk ADHD adolescents
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.
Drug: mixed amphetamine salts-extended release (MAS-XR)
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.
Other Name: AdderallXR

Placebo Comparator: HR-P - High-risk ADHD on Placebo
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.
Drug: Placebo
Pills with no medication in it

No Intervention: HC (Healthy Controls)
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).



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Baseline-endpoint change in uncinate fasciculus white matter integrity by DTI [ Time Frame: Baseline and up to 12 weeks ]
    Change in uncinate fasciculus white matter integrity will be determined by contrasting baseline and endpoint fractional anisotropy using diffusion tensor imaging (DTI).

  2. 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 ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02478788


Contacts
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Contact: Robert McNamara, PhD 513-558-5601 robert.mcnamara@uc.edu

Locations
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United States, Ohio
University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Leah Fleischer    513-558-3674    fleisclm@ucmail.uc.edu   
Principal Investigator: Robert K McNamara, PhD         
Principal Investigator: Melissa P DelBello, MD, MS         
Sponsors and Collaborators
University of Cincinnati
National Institute of Mental Health (NIMH)
Investigators
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Study Director: Robert McNamara, PhD University of Cincinnati

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Responsible Party: Melissa Delbello, Academic Medical Director, University of Cincinnati
ClinicalTrials.gov Identifier: NCT02478788     History of Changes
Other Study ID Numbers: DelBello/McNamara Neuroimaging
R01MH097818-01A1 ( U.S. NIH Grant/Contract )
First Posted: June 23, 2015    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: June 2015

Keywords provided by Melissa Delbello, University of Cincinnati:
ADHD

Additional relevant MeSH terms:
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Amphetamine
Disease
Bipolar Disorder
Attention Deficit Disorder with Hyperactivity
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Attention Deficit and Disruptive Behavior Disorders
Neurodevelopmental Disorders
Central Nervous System Stimulants
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors