Intermittent Explosive DisorderPhase 4NCT02048241
Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder
A Phase 4 study testing Parent Management Training and Intuniv in people with Intermittent Explosive Disorder and Childhood Aggression, run by New York State Psychiatric Institute at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Intermittent Explosive Disorder, Childhood Aggression, Oppositional Defiant Disorder
- What is being tested?
- Parent Management Training and Intuniv
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Dec 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 19Show fewer
- 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)
- normal electrocardiogram
- normal vital signs
- no history of intolerance of guanfacine.
- 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
Who cannot join
- 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)
Show all 21Show fewer
- 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
- Patients who meet criteria for Major Depression in pre-puberty will not be eligible for this study.
- 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.
- Any other history of cardiovascular dysfunction
- Positive Urine Toxicology
- Children who have experienced prior adverse effects (physical or psychological) to either Tenex or clonidine
- Any child who previously received Tenex and either did not tolerate it, or failed to respond to an adequate trial
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
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.
Read the 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.
- Conditions
- Intermittent Explosive Disorder, Childhood Aggression, Oppositional Defiant Disorder, Attention Deficit Disorder
- Being tested
- Parent Management Training, Placebo, Intuniv
- Keywords
- childhood, temper, explosive, aggression, tantrums, oppositional, defiant, conduct, disruptive, emotional dysregulation, special education
- Medical subject headings
- Disruptive, Impulse Control, and Conduct Disorders, Oppositional Defiant Disorder, Attention Deficit Disorder with Hyperactivity, Aggression, Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parent Management TrainingBehavioural
Also called PMT
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.
PlaceboOther
Weekly dispensation of pills matching Intuniv but without the active medication
IntunivDrug
Also called Extended release Guanfacine
Weekly administration of medication in doses as per protocol
| Study group | Role | What they receive |
|---|---|---|
| Placebo plus Parent Management Training | Other | Pills matching Intuniv Tablets without active medication combined with weekly Parent Management Training Receives: 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 Receives: Behavioral: Parent Management Training; Drug: Intuniv |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2014 (estimated)
- Study startJul 2011
- Primary completionNov 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Intermittent Explosive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Shire
- Responsible party
- Principal investigator, Stephen Donovan, New York State Psychiatric Institute
- Investigators
- Stephen J Donovan, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02048241
- Sponsor's protocol ID
- #6068
- Status last verified
- Jun 2018
- First submitted
- 13 Dec 2012
- Last updated
- 13 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intuniv vs Placebo in the Treatment of Childhood Intermittent Explosive Disorder
- ClinicalTrials.gov ID
- NCT02048241
- Acronym / sponsor ID
- #6068
- Conditions
- Intermittent Explosive Disorder, Childhood Aggression, Oppositional Defiant Disorder, Attention Deficit Disorder
- Keywords
- childhood, temper, explosive, aggression, tantrums, oppositional, defiant, conduct
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Shire
- Study start
- Jul 2011 (actual)
- Primary completion
- Nov 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 29 Jan 2014 (estimated)
- Results
- Posted 6 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo plus Parent Management Training | Other | Behavioral: Parent Management Training, Other: PlaceboPills matching Intuniv Tablets without active medication combined with weekly Parent Management Training |
| Intuniv plus Parent Management Training | Experimental | Behavioral: Parent Management Training, Drug: IntunivAdministration 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 |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- Age 6-12
- Meets DSM-IV TR Criteria for Intermittent Explosive Disorder
- Modified Overt Aggression Scale (MOAS) score > 15
- Parent and child willing to consent to study
- Inadequate response to psycho-social interventions (including school interventions)
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parent Management TrainingAlso: PMTThis 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. | Behavioural | Intuniv plus Parent Management Training, Placebo plus Parent Management Training |
| PlaceboWeekly dispensation of pills matching Intuniv but without the active medication | Other | Placebo plus Parent Management Training |
| IntunivAlso: Extended release GuanfacineWeekly administration of medication in doses as per protocol | Drug | Intuniv plus Parent Management Training |
Primary outcome
Number of Participants That Were Responders
Time frame: up to 8 weeks
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Columbia University Clinical Trials linkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen J Donovan, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Parent Management Training and Intuniv in people with Intermittent Explosive Disorder and Childhood Aggression, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Were Responders (time frame: up to 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2018.