Clinical trial NCT03638466: Exploratory fMRI Study on the Treatment for Impulsive Aggression in Children With ADHD
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Impulsive Aggression
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-20
Enrollment: 7
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multi-center, double-blind, randomized (1:1), placebo-controlled, parallel-group, 2-arm study
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study was 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 was 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 were recruited in this study. The PSAP is a behavioral aggression test used to evaluate behavioral response related to impulsive aggression. The task was 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 were also measured using magnetic resonance spectroscopy (MRS).

Additionally, the improvement and severity in impulsive aggression behaviors were assessed using validated scales.

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) 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).

Primary outcomes:
measure: Aggression-related Change in the Whole Brain in BOLD (Blood Oxygenation Level-dependent) Signal fMRI Contrast in Response to the PSAP Task
timeFrame: Baseline/Visit 2 (Day -5) to Visit 5 (Day 28) for a total of 4 weeks.
measure: Provocation Event - Related Change in the Whole Brain in BOLD Signal fMRI Contrast in Response to the PSAP Task
timeFrame: Baseline/Visit 2 (Day -5) to Visit 5 (Day 28) for a total of 4 weeks.
measure: Effect of SPN-810 on the Aggressions Score
timeFrame: Baseline/Visit 2 (Day -5) to Visit 5 (Day 28) for a total of 4 weeks.
Secondary outcomes:
measure: Effect of SPN-810 on GABA and Glutamate Levels Using Magnetic Resonance Spectroscopy (MRS)
timeFrame: Baseline/Visit 2 (Day -5) to Visit 5 (Day 28) for a total of 4 weeks.
Other outcomes:
measure: Effect of SPN-810 on Impulsive Aggression Measured by the Clinical Global Impression-Severity (CGI-S) Scale
timeFrame: From Visit 1 (Day -30) to two time points: Visit 4 (Day 21) and Visit 6 (Day 35).
measure: Effect of SPN-810 on Impulsive Aggression Measured by the Clinical Global Impression-Improvement (CGI-I) Scale
timeFrame: Visit 4 (Day 21) and Visit 6 (Day 35), for a total of 2 weeks.
measure: Effect of SPN-810 on the Retrospective-Modified Overt Aggression Scale (R-MOAS) Score
timeFrame: Visit 1 (Day -30) to Visit 4 (Day 21) and Visit 6 (Day 35).
Locations:
city: Lakeland
country: United States
facility: Meridien Research aka Florida Clinical Research Center, LLC
state: Florida
city: Maitland
country: United States
facility: Florida Clinical Research Center, LLC.
state: Florida
city: Tampa
country: United States
facility: University of South Florida- Dept. of Psychiatry and Neurosciences
state: Florida
Study officials:
References:
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.
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.