Trial of Aripiprazole in the Treatment of CD in Adolescents

Study Overview
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Brief Summary
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The proposed study will be a 6-week open label study evaluating aripiprazole in the treatment of 12 male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder. The initial dose depending on the weight of the patient will be as follows: < 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; > 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). For the first two weeks of the study, the dose will be flexible based on response and tolerance and thereafter will remain fixed.

Detailed Description
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The use of atypical antipsychotics in children began in 1992 with several small case series with clozapine. Since that time, five other atypical agents, risperidone, olanzapine, quetiapine, ziprasidone and aripiprazole have been introduced into the US market. The newer atypical agents are not associated with agranulocytosis that has limited the usefulness of clozapine. Among the atypical antipsychotics, risperidone has remained the most extensively studied in children and adolescents, for a variety of problems, including Tourette's disorder, conduct disorder, schizophrenia, aggression, and pervasive development disorder. Risperidone has been shown to be an effective treatment in many of these disorders. However, weight gain, hyperprolactinemia, and extrapyramidal symptoms (EPS) are troublesome adverse effects more commonly associated with risperidone such that the drug's utility in this aged patient population is limited. We expect that the utility of aripiprazole in treating the pediatric population will not be limited by adverse effects like the other atypical antipsychotics.

Official Title
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Open Label Trial of Aripiprazole in the Treatment of CD in Adolescents

Conditions
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Conduct Disorder

Intervention / Treatment
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* Drug: Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male post-pubertal adolescents (13-17 years, Tanner Stage 4) diagnosed with conduct disorder. Exclusion Criteria: Clinically significant laboratory and/or ECG abnormalities Pre-existing health conditions that would compromise patient safety Mental retardation Previous use of aripiprazole Active psychosis

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Adolescent Conduct Disorder Males<br>All subjects were male and had a diagnosis of conduct disorder. All subjects were offered treatment with aripiprazole. | Drug: Aripiprazole<br>* The initial dose depending on the weight of the patient will be as follows: < 25 kg = 1 mg/d; 25-50 kg = 2 mg/d; 50-70 kg = 5 mg/d; > 70 kg = 10 mg/d (Data on File, 2003, Bristol-Myers Squibb). Thereafter the dose will be flexible based on response and tolerance for the duration of the 6 week study. All subjects initially received either a 5 or 10 mg/d (7.0 ± 2.6 mg/d) dose of aripiprazole. Thereafter the dose was individualized based on response and tolerance. Maximum dose was 20 mg.<br>* Other names: Abilify;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Outcome Efficacy Measure: Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) | Rating of Aggression Against People and/or Property Scale (RAAPP) (Kemph et al 1993) is a global rating scale of aggression completed by clinicians. Score given based on following severity scale with subject assigned 1 number: Intolerable behavior-frequently physically attacks others and destroys property (5); Severe-occasionally physically attacks people and destroys property (4); Moderately 21); and No aggressiveness reported (1). A minimum score of 1 is best and a maximum score of 5 is worst. There are no subscale scores. | 6 weeks | 
| Overt Aggression Scale-Modified (OAS-M) | OAS-M divides aggressions into 4 subtypes: 1) verbal aggression, 2) property aggression, 3) self aggression (autoaggression), and 4) physical aggression. Each subtype has an initial score ranging from 0 (least aggressive) to 4 (most aggressive). The score for each subscale is further weighed (multiplied) by a constant: verbal scale's constant is 1 (max adjusted score of 4); property scale's constant is 2 (max adjusted score 8); self scale's constant is 3 (max adjusted score 12); and physical scale's constant is 4 (max adjusted score of 16). Within a given scale, 0 is the best score and maximum adjusted scale score is worst. | 6 weeks | 
| Children's Aggression Scale-Parent Version | CAS-P is a 33 item scale representing 5 domains of aggression: Items in a domain were computed based on two reference points. The first was based on a 5 point frequency range with 0 being best (never) and 4 (> 10 times being) worst. These same items were then adjusted such that more severe acts would be weighted more heavily compared to less severe aggressive behaviors. Within a domain, 0 was the best score. Worst score for the various aggression domains were: Verbal 26.16, Against Objects and Animals 11.8, Provoked 15.84, Initiated 17.84, and Use of Weapons 13.16. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measures Were the Clinical Global Impression-Severity (CGI-S) Scale (NIMH, 1985a). | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Possible ratings are: 1. Normal, not at all ill; 2. Borderline mentally ill, 3. Mildly ill; 4. Moderately ill; 5. Markedly ill; 6. Severely ill; or 7. Among the most extremely ill patients. | 6 weeks | 
| Secondary Outcome Measures Were the Clinical Global Impression--Improvement (CGI-I) Scales (NIMH, 1985a). | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1. Very much improved; 2. Much improved; 3. Minimally improved; 4. No change; 5. Minimally worse; 6. Much worse; or 7. Much worse) | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aripiprazole