search
Back to results

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

Primary Purpose

Attention Deficit Hyperactivity Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
mixed amphetamine salts-extended release (MAS-XR)
Placebo
Sponsored by
University of Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Attention Deficit Hyperactivity Disorder focused on measuring ADHD

Eligibility Criteria

10 Years - 18 Years (Child, Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Placebo Comparator

No Intervention

Arm Label

LR-MAS - Low-risk ADHD adolescents

HR-MAS - High-risk ADHD adolescents

HR-P - High-risk ADHD on Placebo

HC (Healthy Controls)

Arm 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.

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.

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
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).

Full Information

First Posted
June 15, 2015
Last Updated
September 19, 2023
Sponsor
University of Cincinnati
Collaborators
National Institute of Mental Health (NIMH)
search

1. Study Identification

Unique Protocol Identification Number
NCT02478788
Brief Title
Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
Acronym
NERF
Official Title
Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
August 2022 (Actual)
Study Completion Date
December 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cincinnati
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Hyperactivity Disorder
Keywords
ADHD

7. Study Design

Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
153 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LR-MAS - Low-risk ADHD adolescents
Arm Type
Experimental
Arm 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.
Arm Title
HR-MAS - High-risk ADHD adolescents
Arm Type
Experimental
Arm 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.
Arm Title
HR-P - High-risk ADHD on Placebo
Arm Type
Placebo Comparator
Arm 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.
Arm Title
HC (Healthy Controls)
Arm Type
No Intervention
Arm 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).
Intervention Type
Drug
Intervention Name(s)
mixed amphetamine salts-extended release (MAS-XR)
Other Intervention Name(s)
AdderallXR
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pills with no medication in it
Primary Outcome Measure Information:
Title
Baseline-endpoint change in prefrontal-amygdala functional connectivity by fMRI.
Description
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.
Time Frame
Baseline and up to 12 weeks
Secondary Outcome Measure Information:
Title
Baseline-endpoint change in uncinate fasciculus white matter integrity by DTI
Description
Change in uncinate fasciculus white matter integrity will be determined by contrasting baseline and endpoint fractional anisotropy using diffusion tensor imaging (DTI).
Time Frame
Baseline and up to 12 weeks
Title
Baseline-endpoint change in glutamate (Glu) and N-acetyl aspartate (NAA) concentrations in the prefrontal cortex (BA47) by 1H MRS.
Description
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).
Time Frame
Baseline and up to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert McNamara, PhD
Organizational Affiliation
University of Cincinnati
Official's Role
Study Director
Facility Information:
Facility Name
University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Neuroimaging Study of Risk Factors for Adolescent Bipolar Disorder

We'll reach out to this number within 24 hrs