Trial record 18 of 141 for:    Open Studies | "Aggression"

Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by New York State Psychiatric Institute
Sponsor:
Collaborator:
Shire
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT02048241
First received: December 13, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Intermittent Explosive Disorder
Childhood Aggression
Oppositional Defiant Disorder
Attention Deficit Disorder
Behavioral: Parent Management Training
Other: Placebo
Drug: Intuniv
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Responder vs Non-Responder Assessment Form [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    Response is at least a 70% reduction from baseline in both the Modified Over Aggression Scale (MOAS) score and the score on the Six Hostility Items of the Hopkins Symptoms Checklist (SCL 6). Any other change in MOAS and SCL 6 constitutes non-response.


Secondary Outcome Measures:
  • Percent change in score on the Attention Deficit Hyperactivity Disorder [ADHD] Rating Scale [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
    This ADHD rating scale yields a score by rating each ADHD symptom on a scale of 0 to 3, with 0 being never and 3 being very often. The percent change is obtained by subtracting the baseline score from the end of study score and dividing by the baseline score.

  • Percent change in the Modified Overt Aggression Scale [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    This version of the Modified Overt Aggression Scale measures the frequency and severity of explosive episodes during the previous week using all available informants. It yield a number that combines the frequency and severity of episodes. The percent change is obtained by subtracting the baseline score from the end of study score and dividing by the baseline score.

  • Percent Change in the Score on Hostility Subscale of the Hopkins Symptom Checklist [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    This scale probes for irritability: impatience, intolerance and poor anger control indicating a disposition for angry responses. The percent change is obtained by subtracting the baseline score from the end of study score and dividing by the baseline score.


Estimated Enrollment: 40
Study Start Date: July 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo plus Parent Management Training
Pills matching Intuniv Tablets without active medication combined with weekly Parent Management Training
Behavioral: Parent Management Training
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.
Other Name: PMT
Other: Placebo
Weekly dispensation of pills matching Intuniv but without the active medication
Experimental: Intuniv plus Parent Management Training
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
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.
Other Name: PMT
Drug: Intuniv
Weekly administration of medication in doses as per protocol
Other Name: Extended release Guanfacine in doses of 1, 2, 3, 4 mgs as per protocol

Detailed 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.

  Eligibility

Ages Eligible for Study:   6 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 6-12
  2. Meets DSM-IV TR Criteria for Intermittent Explosive Disorder

    1. several discreet episodes of failure to resist aggressive impulses that result in serious assaultive acts or destruction of property
    2. the degree of aggressiveness is grossly out of proportion to any precipitating psychosocial stressors
    3. the aggressive episode is not better accounted for by another mental disorder
    4. duration of at least six months
    5. impairment in home, peer relations and / or school
  3. Modified Overt Aggression Scale (MOAS) score > 15
  4. Parent and child willing to consent to study
  5. Inadequate response to psycho-social interventions (including school interventions)
  6. Medically healthy with

    1. weight > 55 lb (25 kg)
    2. body mass index < 35
    3. normal blood pressure as defined by National Heart Lung and Blood Institute (below 95th percentile for age height and weight)
    4. normal response to orthostatic changes (no persistent fall in systolic/diastolic BP > 20/10 mm Hg within 3 minutes of assuming the upright position)
    5. normal electrocardiogram
    6. normal vital signs
    7. no history of intolerance of guanfacine.
  7. If on another medication, willingness to discontinue if medication is judged ineffective after adequate trial or to remain on a constant optimized dose if it is partially effective

Exclusion Criteria:

  1. Current Treatment with another alpha 2 blocker e.g. clonidine
  2. Puberty
  3. Meets criteria for Pervasive Developmental Disorder or Childhood schizophrenia
  4. MOAS score > 50
  5. weight < 55 lb or body mass index > 35
  6. hypertension (Blood Pressure above 95th percentile for age height and weight)
  7. Chronic hypotension (Blood Pressure at or below 5th percentile for age height and weight)
  8. Orthostatic Hypotension fall in systolic/diastolic BP > 20/10 mm Hg within 3 minutes of assuming the upright position
  9. QTc interval of > 440 milliseconds; Bradycardia; heart block diagnosed
  10. history of seizure during the past 2 years (exclusive of febrile seizures)
  11. Patients who had taken an investigational drug within 28 days
  12. Intelligence Quotient < 70
  13. Physical exam, EKG or laboratory results with any other significant abnormalities until reviewed by medicine.
  14. Active suicidal or homicidal ideation or history of suicide attempts
  15. Unequivocal manic or hypomanic Episode
  16. Patients who meet criteria for Major Depression in pre-puberty will not be eligible for this study.
  17. Axis I disorders that are current, severe and uncontrolled. Children with moderate Axis I pathology will be evaluated on a case by case basis and excluded if the other diagnosis is not ADHD but could still be the cause of the temper dyscontrol and the treatment is judged substandard.
  18. Any other history of cardiovascular dysfunction
  19. Positive Urine Toxicology
  20. Children who have experienced prior adverse effects (physical or psychological) to either Tenex or clonidine
  21. Any child who previously received Tenex and either did not tolerate it, or failed to respond to an adequate trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02048241

Contacts
Contact: Stephen J Donovan, MD 646 774 8078 sd45@columbia.edu
Contact: Carrie Davies, BA 646 774 8081 Daviesc@nyspi.columbia.edu

Locations
United States, New York
New York State Psychiatric Institute Recruiting
New York, New York, United States, 10032
Principal Investigator: Stephen J Donovan, MD         
Sponsors and Collaborators
New York State Psychiatric Institute
Shire
Investigators
Principal Investigator: Stephen J Donovan, MD New York State Psychiatric Institute
  More Information

Additional Information:
No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT02048241     History of Changes
Other Study ID Numbers: #6068
Study First Received: December 13, 2012
Last Updated: January 27, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:
aggression
childhood
temper
explosive
tantrums
oppositional
defiant
conduct
disruptive
emotional dysregulation
special education

Additional relevant MeSH terms:
Aggression
Impulse Control Disorders
Attention Deficit and Disruptive Behavior Disorders
Attention Deficit Disorder with Hyperactivity
Behavioral Symptoms
Mental Disorders
Mental Disorders Diagnosed in Childhood
Guanfacine
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014