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

University of Cincinnati

Status and phase: Completed; Phase 4

Conditions: Attention Deficit Hyperactivity Disorder

Treatments: Drug: mixed amphetamine salts-extended release (MAS-XR); Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02478788

R01MH097818-01A1 (U.S. NIH Grant/Contract)

DelBello/McNamara Neuroimaging

Details and patient eligibility

About

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.

Full 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).

Enrollment: 153 patients

Sex: All

Ages: 10 to 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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153 participants in 4 patient groups, including a placebo group

LR-MAS - Low-risk ADHD adolescents

Experimental group

Description:

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.

Treatment:

Drug: mixed amphetamine salts-extended release (MAS-XR)

HR-MAS - High-risk ADHD adolescents

Experimental group

Description:

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.

Treatment:

Drug: mixed amphetamine salts-extended release (MAS-XR)

HR-P - High-risk ADHD on Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

HC (Healthy Controls)

No Intervention group

Description:

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).