Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder

NCT02048241 | Completed Phase 4 Results DMC

• 1 other identifier: #6068
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Intermittent Explosive Disorder; Childhood Aggression; Oppositional Defiant Disorder; Attention Deficit Disorder

Keywords

childhood; temper; explosive; aggression; tantrums; oppositional; defiant; conduct; disruptive; emotional dysregulation; special education

Outcome Measures

Primary Outcomes (1)

• 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.

  up to 8 weeks

Study Arms (2)

Placebo plus Parent Management Training

OTHER

Pills matching Intuniv Tablets without active medication combined with weekly Parent Management Training

Behavioral: Parent Management Training; Other: Placebo

Intuniv plus Parent Management Training

EXPERIMENTAL

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

Interventions

Parent Management Training BEHAVIORAL

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

Intuniv plus Parent Management Training; Placebo plus Parent Management Training

Placebo OTHER

Weekly dispensation of pills matching Intuniv but without the active medication

Placebo plus Parent Management Training

Intuniv DRUG

Weekly administration of medication in doses as per protocol

Also known as: Extended release Guanfacine

Intuniv plus Parent Management Training

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 6-12
• Meets DSM-IV TR Criteria for Intermittent Explosive Disorder
• several discreet episodes of failure to resist aggressive impulses that result in serious assaultive acts or destruction of property
• the degree of aggressiveness is grossly out of proportion to any precipitating psychosocial stressors
• the aggressive episode is not better accounted for by another mental disorder
• duration of at least six months
• impairment in home, peer relations and / or school
• Modified Overt Aggression Scale (MOAS) score \> 15
• Parent and child willing to consent to study
• Inadequate response to psycho-social interventions (including school interventions)
• Medically healthy with
• weight \> 55 lb (25 kg)
• body mass index \< 35
• normal blood pressure as defined by National Heart Lung and Blood Institute (below 95th percentile for age height and weight)
• normal response to orthostatic changes (no persistent fall in systolic/diastolic BP \> 20/10 mm Hg within 3 minutes of assuming the upright position)

You may not qualify if:

• Current Treatment with another alpha 2 blocker e.g. clonidine
• Puberty
• Meets criteria for Pervasive Developmental Disorder or Childhood schizophrenia
• MOAS score \> 50
• weight \< 55 lb or body mass index \> 35
• hypertension (Blood Pressure above 95th percentile for age height and weight)
• Chronic hypotension (Blood Pressure at or below 5th percentile for age height and weight)
• Orthostatic Hypotension fall in systolic/diastolic BP \> 20/10 mm Hg within 3 minutes of assuming the upright position
• QTc interval of \> 440 milliseconds; Bradycardia; heart block diagnosed
• history of seizure during the past 2 years (exclusive of febrile seizures)
• Patients who had taken an investigational drug within 28 days
• Intelligence Quotient \< 70
• Physical exam, EKG or laboratory results with any other significant abnormalities until reviewed by medicine.
• Active suicidal or homicidal ideation or history of suicide attempts
• Unequivocal manic or hypomanic Episode

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• Shire: collaborator

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Links

• Columbia University Clinical Trials link

MeSH Terms

Conditions

Disruptive, Impulse Control, and Conduct Disorders; Oppositional Defiant Disorder; Attention Deficit Disorder with Hyperactivity; Aggression; Behavior

Interventions

Guanfacine

Condition Hierarchy (Ancestors)

Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Social Behavior

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids

Results Point of Contact

• Title: Stephen J. Donovan, MD
• Organization: New York State Psychiatric Institute

sd45@columbia.edu

646-774-8078

Study Officials

• Stephen J Donovan, MD

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Psychiatrist

Study Record Dates

• First Submitted: December 13, 2012
• First Posted: January 29, 2014
• Study Start: July 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 13, 2018
• Results First Posted: November 6, 2017

Record last verified: 2018-06

Locations

US (1)