A Phase 4 interventional study of Parent Management Training and Placebo in Intermittent Explosive Disorder, Childhood Aggression and Oppositional Defiant Disorder, sponsored by New York State Psychiatric Institute. Completed at 1 site in United States. Open to participants aged 6 Years to 12 Years. Per ClinicalTrials.gov, last updated 2018-06-13.
Sponsored by New York State Psychiatric Institute · Phase 4, Interventional, and Treatment
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.
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.
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This study's enrollment of 11 is below the median of 72 across 1,207 interventional studies indexed under Attention Deficit Disorder with Hyperactivity.
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Meets DSM-IV TR Criteria for Intermittent Explosive Disorder
Medically healthy with
Exclusion Criteria:
Pills matching Intuniv Tablets without active medication combined with weekly Parent Management Training
Behavioral: Parent Management Training · Other: Placebo
Administration of Intuniv in increasing doses from 1 mg to 2 mgs to 3 mgs to 4 mgs as tolerated over a period of 4-6 weeks, combined with weekly Parent Management Training
Behavioral: Parent Management Training · Drug: Intuniv
This is a psychological treatment that focuses on decreasing tantrums and outbursts by reducing the ability of the tantrum to coerce parents into giving in to the demand that precipitated the tantrum.
Also known as: PMT
Weekly dispensation of pills matching Intuniv but without the active medication
Weekly administration of medication in doses as per protocol
Also known as: Extended release Guanfacine
Number of Participants That Were Responders
Overall response to treatment is defined as at least a 70% decline in both the Modified Overt Aggression Scale (MOAS) score and the Symptom Checklist-6 (SCL-6) from randomization to end of study. The MOAS measures the severity of explosive overt aggression. The score can range from 0 (no overt aggressive) and it has no theoretical upper limit (incidents could be too many to count). The higher the score, the more serious the aggression; the lower the score, the less serious the aggression. Response to treatment is defined as a 70% or more reduction in the MOAS at the end of the study. The SCL-6 uses 6 subscale items from the larger SCL that measure hostility or irritability on a scale of 1 (not at all) - 5 (definitely). The raw score ranges from 6 (no irritability) to 30 (severe irritability). The lower the score is, the better the outcome. The % decline vary from 0%-100%. A 70% or more decline in the SCL-6 score at the end of study is a response.
Time frame: up to 8 weeks
| Milestone | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training |
|---|---|---|
| Started | 5 | 6 |
| Completed | 5 | 5 |
| Not completed | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
Overall response to treatment is defined as at least a 70% decline in both the Modified Overt Aggression Scale (MOAS) score and the Symptom Checklist-6 (SCL-6) from randomization to end of study. The MOAS measures the severity of explosive overt aggression. The score can range from 0 (no overt aggressive) and it has no theoretical upper limit (incidents could be too many to count). The higher the score, the more serious the aggression; the lower the score, the less serious the aggression. Response to treatment is defined as a 70% or more reduction in the MOAS at the end of the study. The SCL-6 uses 6 subscale items from the larger SCL that measure hostility or irritability on a scale of 1 (not at all) - 5 (definitely). The raw score ranges from 6 (no irritability) to 30 (severe irritability). The lower the score is, the better the outcome. The % decline vary from 0%-100%. A 70% or more decline in the SCL-6 score at the end of study is a response.
| Participants | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training |
|---|---|---|
| Number of Participants That Were Responders | 0 | 5 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo Plus Parent Management Training | 0/5 (0%) | 0/5 (0%) | 2/5 (40%) |
| Intuniv Plus Parent Management Training | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Event | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training |
|---|---|---|
| FatigueGeneral disorders | 0/5 | 3/6 |
| InsomniaPsychiatric disorders | 1/5 | 0/6 |
| IrritabilityPsychiatric disorders | 1/5 | 0/6 |
| Age, Categorical(Participants) | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training | Total |
|---|---|---|---|
| <=18 years | 5 | 6 | 11 |
| Between 18 and 65 years | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training | Total |
|---|---|---|---|
| Female | 0 | 1 | 1 |
| Male | 5 | 5 | 10 |
| Race/Ethnicity, Customized(Participants) | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training | Total |
|---|---|---|---|
| White | 2 | 1 | 3 |
| African American | 1 | 2 | 3 |
| Hispanic | 2 | 3 | 5 |
| Region of Enrollment(Participants) | Placebo Plus Parent Management Training | Intuniv Plus Parent Management Training | Total |
|---|---|---|---|
| United States | 5 | 6 | 11 |
This study is completed, as verified in Jun 2018. You cannot join it, but the record below documents what was studied.
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