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Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With Attention-Deficit/Hyperactivity Disorder

Primary Purpose

Attention Deficit Hyperactivity Disorder (ADHD), Impulsive Aggression

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Functional Magnetic Resonance Imaging (fMRI)
Magnetic Resonance Spectroscopy (MRS)
Point Subtraction Aggression Paradigm (PSAP) Task
SPN-810
Placebo
Sponsored by
Supernus Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Attention Deficit Hyperactivity Disorder (ADHD)

Eligibility Criteria

8 Years - 12 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Otherwise healthy male or female subjects, aged 8-12 years, inclusive, at the time of screening with primary diagnosis of ADHD and currently receiving monotherapy treatment with an optimized US Food and Drug Administration (FDA)-approved ADHD medication.
  • Impulsive aggression (IA) will be confirmed at screening using the R-MOAS and the Vitiello Aggression Scale.

Exclusion Criteria:

  • Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia or related disorder, personality disorder, Tourette's disorder, fetal alcohol syndrome, or psychosis not otherwise specified.
  • Currently meeting DSM criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder.
  • Known or suspected IQ <70, pregnancy, substance or alcohol abuse.
  • Known history of implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal shunt, cardiac pacemaker, orthodontic braces, or implanted medication port. Visual and hearing (≥25 dB) impairment.
  • Pre-existing medical or psychological conditions that preclude being in the MRI scanner (e.g., claustrophobia, morbid obesity, or marked anxiety about the procedure).

Sites / Locations

  • Meridien Research aka Florida Clinical Research Center, LLC
  • Florida Clinical Research Center, LLC.
  • University of South Florida- Dept. of Psychiatry and Neurosciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Single dose of SPN-810

Placebo

Arm Description

Subjects will be treated with medium dose of SPN-810

Subjects will be treated with a matching Placebo

Outcomes

Primary Outcome Measures

BOLD fMRI contrast (beta value) at baseline and after 4 weeks of treatment with SPN-810 in response to the aggression task. The z-score acquired during resting state fMRI before and after the treatment with SPN-810.
BOLD fMRI contrast (neural activation) will be collected during the PSAP behavioral aggression task, while playing the game. The participant will play a computer game in which they can steal points (simulating an aggressive behavior) or have points stolen by the opponent. In addition, imaging data will be collected at resting state to understand the connectivity between regions of interest before and after the aggression task.

Secondary Outcome Measures

Changes in GABA and Glutamate levels from baseline to the end of treatment
During the MRI scan, imaging data will be obtained while participants are able to listen to music. GABA and Glutamate signals measured using magnetic resonance spectroscopy (MRS) from two brain regions (anterior cingulate cortex and amygdala) will be used to quantify the two neurotransmitters.

Full Information

First Posted
August 16, 2018
Last Updated
December 21, 2021
Sponsor
Supernus Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03638466
Brief Title
Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With Attention-Deficit/Hyperactivity Disorder
Official Title
Exploratory Neuroimaging Study to Evaluate the Effect on Brain Activity of SPN-810 for Impulsive Aggression (IA) in Patients With Attention-Deficit/Hyperactivity Disorder (ADHD) in Conjunction With Standard ADHD Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Financial decision
Study Start Date
May 30, 2019 (Actual)
Primary Completion Date
November 7, 2019 (Actual)
Study Completion Date
November 7, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Supernus Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to evaluate the effect of 4-week SPN-810 treatment on brain functioning in patients aged 8-12 years with ADHD and associated feature of impulsive aggression (IA). This will be achieved using functional magnetic resonance imaging (fMRI) in conjunction with the point subtraction aggression paradigm (PSAP) Task, a behavioral aggression paradigm in which subjects are provoked by having money indirectly taken from them by a fictitious opponent, simulating an aggression response.
Detailed Description
Approximately 30 subjects aged 8-12 diagnosed with ADHD and associated feature of IA will be recruited in this study. The PSAP is a behavioral aggression test used to evaluate behavioral response related to impulsive aggression. The task will be combined with functional MRI to evaluate the change in brain activity measured as BOLD signal (blood oxygenation level-dependent) from baseline to the end of the treatment with SPN-810. The level of neurotransmitters Glutamate and GABA will also be measured using magnetic resonance spectroscopy (MRS). Additionally, the improvement and severity in impulsive aggression behaviors will be assessed using validated scales.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Attention Deficit Hyperactivity Disorder (ADHD), Impulsive Aggression

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A multi-center, double-blind, randomized (1:1), placebo-controlled, parallel-group, 2-arm study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single dose of SPN-810
Arm Type
Active Comparator
Arm Description
Subjects will be treated with medium dose of SPN-810
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects will be treated with a matching Placebo
Intervention Type
Diagnostic Test
Intervention Name(s)
Functional Magnetic Resonance Imaging (fMRI)
Intervention Description
Neural brain activity measured by fMRI
Intervention Type
Diagnostic Test
Intervention Name(s)
Magnetic Resonance Spectroscopy (MRS)
Intervention Description
Glutamate and GABA levels measured by MRS
Intervention Type
Behavioral
Intervention Name(s)
Point Subtraction Aggression Paradigm (PSAP) Task
Intervention Description
Aggression score measured by the PSAP task
Intervention Type
Drug
Intervention Name(s)
SPN-810
Intervention Description
Treatment of SPN-810 36 mg on neuronal brain activity, GABA and Glutamate levels and on the aggression score
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Treatment of placebo on neuronal brain activity, GABA and Glutamate levels and on the aggression score
Primary Outcome Measure Information:
Title
BOLD fMRI contrast (beta value) at baseline and after 4 weeks of treatment with SPN-810 in response to the aggression task. The z-score acquired during resting state fMRI before and after the treatment with SPN-810.
Description
BOLD fMRI contrast (neural activation) will be collected during the PSAP behavioral aggression task, while playing the game. The participant will play a computer game in which they can steal points (simulating an aggressive behavior) or have points stolen by the opponent. In addition, imaging data will be collected at resting state to understand the connectivity between regions of interest before and after the aggression task.
Time Frame
9 weeks
Secondary Outcome Measure Information:
Title
Changes in GABA and Glutamate levels from baseline to the end of treatment
Description
During the MRI scan, imaging data will be obtained while participants are able to listen to music. GABA and Glutamate signals measured using magnetic resonance spectroscopy (MRS) from two brain regions (anterior cingulate cortex and amygdala) will be used to quantify the two neurotransmitters.
Time Frame
9 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Otherwise healthy male or female subjects, aged 8-12 years, inclusive, at the time of screening with primary diagnosis of ADHD and currently receiving monotherapy treatment with an optimized US Food and Drug Administration (FDA)-approved ADHD medication. Impulsive aggression (IA) will be confirmed at screening using the R-MOAS and the Vitiello Aggression Scale. Exclusion Criteria: Current or lifetime diagnosis of epilepsy, major depressive disorder, bipolar disorder, schizophrenia or related disorder, personality disorder, Tourette's disorder, fetal alcohol syndrome, or psychosis not otherwise specified. Currently meeting DSM criteria for autism spectrum disorder, pervasive developmental disorder, obsessive-compulsive disorder, post-traumatic stress disorder. Known or suspected IQ <70, pregnancy, substance or alcohol abuse. Known history of implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal shunt, cardiac pacemaker, orthodontic braces, or implanted medication port. Visual and hearing (≥25 dB) impairment. Pre-existing medical or psychological conditions that preclude being in the MRI scanner (e.g., claustrophobia, morbid obesity, or marked anxiety about the procedure).
Facility Information:
Facility Name
Meridien Research aka Florida Clinical Research Center, LLC
City
Lakeland
State/Province
Florida
ZIP/Postal Code
33805
Country
United States
Facility Name
Florida Clinical Research Center, LLC.
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
University of South Florida- Dept. of Psychiatry and Neurosciences
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9046983
Citation
Cherek DR, Moeller FG, Schnapp W, Dougherty DM. Studies of violent and nonviolent male parolees: I. Laboratory and psychometric measurements of aggression. Biol Psychiatry. 1997 Mar 1;41(5):514-22. doi: 10.1016/s0006-3223(96)00059-5.
Results Reference
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PubMed Identifier
26292852
Citation
Bubenzer-Busch S, Herpertz-Dahlmann B, Kuzmanovic B, Gaber TJ, Helmbold K, Ullisch MG, Baurmann D, Eickhoff SB, Fink GR, Zepf FD. Neural correlates of reactive aggression in children with attention-deficit/hyperactivity disorder and comorbid disruptive behaviour disorders. Acta Psychiatr Scand. 2016 Apr;133(4):310-23. doi: 10.1111/acps.12475. Epub 2015 Aug 21.
Results Reference
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Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With Attention-Deficit/Hyperactivity Disorder

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