Clinical Trials Logo

Clinical Trial Summary

Children with explosive aggression are often rejected by their peers, placed in special classroom, and contribute to family discord. When psychotherapy and family therapy is unsuccessful, medications are often used. Current medications are stimulants (e.g. methylphenidate, dextroamphetamine), anticonvulsants (e.g. Divalproex) and antipsychotics (olanzapine, risperidone). At this time, the available medications are of limited usefulness, either because they do not always work or because they have side effects such as weight gain or insomnia. There is a clear need for new medications to treat explosive aggression when psychotherapy is unsuccessful.

The hypothesis of this study is the medication Intuniv when combined with psychotherapy will be more helpful to children with explosive aggression than placebo combined with psychotherapy. Intuniv is a long acting form of guanfacine, a medication approved by the FDA for treatment of Attention Deficit Hyperactivity Disorder. Intuniv is not a stimulant, nor is it an anticonvulsant, nor is it an antipsychotic.

The children in this study will be between the ages of 6 and 12 and meet Diagnostic and Statistical Manual of Psychiatry Fourth Edition, Text Revision (DSM-IV-TR) criteria for Intermittent Explosive Disorder.


Clinical Trial Description

Aggressive children are often alienated from parents, separated from peers, placed in special education and segregated with other aggressive children. While predatory (i.e. planned, goal directed, reward driven) aggression is not responsive to pharmacologic treatment, non predatory (impulsive, paranoid, irritable) aggression (DSM-IV-TR "Intermittent Explosive Disorder") often is. Intermittent Explosive Disorder is characterized by discrete episodes of failure to resist aggressive impulses resulting in serious assaults or destruction of property. In children, due to their limited ability to damage or hurt others, the seriousness of the aggressive impulses are indicated by (a) the frequency and severity of tantrums (b) the fact that the severity is out of proportion to the provocation, and (c) the intent to damage and hurt is present and (d) this pattern of events causes impairment.

The level of aggression being studied is equivalent to that in moderate to severe Oppositional Defiant Disorder with the severity due to the tantrums rather than passive aggression (Modified Overt Aggression Score between 15-50). For 20 years a blood pressure medication, guanfacine (Tenex), has also been used for impulse control (e.g. in Attention Deficit Disorder, in Tourette's Syndrome) and to calm the sympathetic nervous system when it is hyper-aroused (e.g. in opiate and nicotine withdrawal]. Both impulsivity and hyper arousal can also promote intermittent explosive aggression. If guanfacine treats impulsivity and hyper arousal, it is logical to ask if guanfacine can treat intermittent explosive aggression.

Shire Pharmaceuticals modified the guanfacine molecule to create a long acting preparation (Intuniv) that the FDA recently judged safe and effective for Attention Deficit Hyperactivity Disorder (ADHD) in children ages 6-17. Secondary analysis of data from the pivotal studies that led to this indication revealed that in ADHD children, Intuniv also reduced oppositional-defiant symptoms. Better impulse control (these were all ADHD children) and/or decreased sympathetic arousal (common to all intermittent explosive aggression) are plausible explanations.

This Investigator Sponsor Protocol (ISP) seeks to replicate prospectively the anti-aggression finding. Since Intuniv could benefit non-ADHD aggressive children, any child with mild to moderate Intermittent Explosive Disorder is eligible. Anti-psychotic and anti-convulsant medications (current treatments for Intermittent Explosive Disorder) have serious side effects (weight gain, metabolic syndrome) and are not always effective. Intuniv is neither a stimulant, nor an antipsychotic, nor an anticonvulsant. Intuniv is not FDA approved for treatment of Intermittent Explosive Disorder.

In addition to medication or placebo, all children will receive a modified form of Parent Management Training, the standard psychotherapy for oppositional symptoms, administered by a child psychiatrist. It addresses the coercive reciprocal social interactions that characterize microenvironment of oppositional children.

Fifty children, ages 6-12 with Intermittent Explosive Disorder will be randomly assigned to eight weeks of double blind Intuniv plus Parent Management Training or placebo Parent Management Training. Titrated over four weeks to a maximum dose of 4 mgs or .09-.12 mgs/kg/day, they will be maintained on that dose for four weeks. At the end of treatment, the treating physician will break the blind and offer open label treatment for eight weeks. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02048241
Study type Interventional
Source New York State Psychiatric Institute
Contact
Status Completed
Phase Phase 4
Start date July 2011
Completion date December 2014

See also
  Status Clinical Trial Phase
Completed NCT03535805 - Transdiagnostic, Cognitive and Behavioral Intervention for in School-aged Children With Emotional and Behavioral Disturbances N/A
Completed NCT02485587 - Arousal-Biofeedback for the Treatment of Aggressive Behavior in Children and Adolescents N/A
Completed NCT00819429 - Supplements and Social Skills Intervention Study N/A
Completed NCT01085305 - The Effectiveness of Parent-Child Interaction Therapy (PCIT) N/A
Completed NCT00250354 - A Study of the Safety and Effectiveness of Risperidone for the Treatment of Conduct Disorder and Other Disruptive Behavior Disorders in Children Ages 5 to 12 With Mild, Moderate, or Borderline Mental Retardation Phase 3
Completed NCT05496140 - Remote School-Home Program to Improve Youth Attention and Behavior in Mexican Students N/A
Completed NCT05425966 - Adapting a Web-Based Professional Development for Mexican School Mental Health Providers Delivering Evidence-Based Intervention for ADHD and ODD N/A
Active, not recruiting NCT05049356 - Symptoms and Mechanisms of Child Psychiatric Disorders
Completed NCT03698240 - Mindfulness-based Program for Children With Disruptive Behavior Disorder N/A
Completed NCT02766101 - Manville Moves: an Exercise Intervention for Behavioral Regulation Among Children With Behavioral Health Challenges N/A
Completed NCT00404911 - Multi-Family Group Therapy for Reducing Behavioral Difficulties in Youth N/A
Completed NCT00192023 - An Italian Study of the Efficacy of Atomoxetine in the Treatment of Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD) and Comorbid Oppositional Defiant Disorder (ODD). Phase 3
Completed NCT03292848 - Trial to Assess the Pharmacokinetics, Safety, Tolerability of Oral Brexpiprazole in Children (6 to <13 Years Old) With Central Nervous System Disorders Phase 1
Recruiting NCT06373484 - Matching Assessment and Treatment for Children With Disruptive Behaviour and Their Parents N/A
Recruiting NCT05637320 - Big Feelings: A Study on Children's Emotions in Therapy N/A
Completed NCT03729154 - Preschool First Step to Success: An Efficacy Replication Study N/A
Completed NCT02281825 - Correlating Real and Virtual World Behavioral Fluctuations in Adolescence N/A
Completed NCT01822392 - On-line Treatment for Conduct Problems N/A
Completed NCT00406354 - Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany Phase 4
Completed NCT02783560 - Behavioral Sleep Intervention in Children With Disruptive Behaviors N/A