Clinical trial NCT02478788: Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
Official title: Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2015-06-23
Enrollment: 153
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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).

Eligibility 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

Primary outcomes:
measure: Baseline-endpoint change in prefrontal-amygdala functional connectivity by fMRI.
timeFrame: Baseline and up to 12 weeks
Secondary outcomes:
measure: Baseline-endpoint change in uncinate fasciculus white matter integrity by DTI
timeFrame: Baseline and up to 12 weeks
measure: Baseline-endpoint change in glutamate (Glu) and N-acetyl aspartate (NAA) concentrations in the prefrontal cortex (BA47) by 1H MRS.
timeFrame: Baseline and up to 12 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Robert McNamara, PhD
role: STUDY_DIRECTOR
References: