Abilify: Efficacy of Aripiprazole Versus Placebo in the Reduction of Aggressive and Aberrant Behavior in Autistic Children

• Sponsor: University of Medicine and Dentistry of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT00468130
• Collaborator: (none)
• Enrollment: 13
• Location: 1
• Arms: 2
• Duration (Months): 42.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Hypothesis: (1) Aripiprazole treatment will be superior to placebo in reducing aggression and irritability in autistic individuals as shown by reductions in the Aberrant Behavior Checklist-irritability subscale.

(2) Aripiprazole treatment will be superior to placebo in the acute treatment of global autism severity.

The purpose of this study is to examine the possible benefit of the medication Aripiprazole in autistic individuals.

Condition or Disease	Intervention/Treatment	Phase
Autism	Drug: Aripiprazole; Drug: Placebos	N/A

Detailed Description

Aripiprazole is an atypical antipsychotic medication which is currently approved for the treatment of schizophrenia in adults. Multiple clinical trials in both children and adults have shown the effectiveness in the treatment of autism with medications like Aripiprazole. This study aims at assessing the effect of aripiprazole vs. placebo treatment on symptoms of irritability and aggression associated with autism, as well as the effect on the global severity of child and adolescent autistic disorder. Children or adolescent outpatients, with age ranges from 5-17, will be enrolled into an 8-week placebo controlled, double blind treatment study. During the 8 weeks, patients will be monitored by the treating psychiatrist. Study assessments will be administered at designated time points.

Study Design

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy of Aripiprazole Versus Placebo in the Reduction of Aggressive and Aberrant Behavior in Autistic Children
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aripiprazole Subjects in the experimental group will receive Aripiprazole	Drug: Aripiprazole; Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects; Other Names: Abilify
Placebo Comparator: Placebo Subjects in the control group will receive sugar pill	Drug: Placebos; Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Clinical Global Impression Improvement (CGI-AD) [Administered weekly, initial and week 8 reported]

   Clinical Global Impression Improvement (CGI)-AD (Guy, 1976). This is a standard rating scale with 7-point global severity and change scales which has been modified for Autistic Disorder. A rating of 2 is given when there is a substantial reduction in symptoms so that a treating clinician would be unlikely to change treatment. A rating of 1 is reserved for patients who become virtually symptom-free. A rating of 3 (minimally improved) on the CGI is defined as slight symptomatic improvement that is not deemed clinically significant. Administration time is approximately 2 minutes. Minimum is 1 and maximum is 5. A lower score indicates improvement, whereas a higher score indicates worsening.

Secondary Outcome Measures

1. Aberrant Behavior Checklist [Administered biweekly, initial and week 8 reported]

   Aberrant Behavior Checklist (ABC) (irritability section) (Aman et al, 1985). The Aberrant Behavior Checklist assesses drug and other treatment effects on mentally retarded individuals. It consists of a five-factor scale comprising 58 items. We will use the Irritability section to assess aggressive and agitated behavior. While the internal consistency, validity and test-retest reliability were reported to be very good, inter-rater reliability was moderate (Aman et al, 1985). The ABC will be filled out by an informant, and then reviewed by the psychiatrist. Administration time is approximately 10 minutes. Maximum is 36, minimum is 0, a lower score indicates improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meets DSM-IV, ADI-R criteria for autistic disorder.

• Age 5-17 years.

• Outpatients

• Parent or legal guardian willing to sign informed consent.

Exclusion Criteria:

• Subject has been diagnosed with a psychotic disorder (such as schizophrenia) or a mood disorder, including depression or bipolar disorder (manic depression).

• Subject has caused visible harm to him/herself.

• Subject has an active seizure disorder or epilepsy (seizures within the past year).

• Subject has an unstable medical illness, including heart disease.

• Subject has experienced brain injury.

• Subject has a history of diabetes.

• Subject reports significant improvement of autism symptoms and behaviors to current medication or other therapies.

• Subject has a history of prior treatment with Aripiprazole of 5 mg/day or higher for 6 weeks.

• Subject lives in a far away area and/or does not have regular access to transportation to the clinical facility.

• Subject is a pregnant female or unwilling to use acceptable contraception if sexually active.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Child and Adolescent Psychiatry, University Behavioral Health Care Building	Piscataway	New Jersey	United States	08854

Sponsors and Collaborators

• University of Medicine and Dentistry of New Jersey

Investigators

• Principal Investigator: Sherie L. Novotny, MD, Child and Adolescent Psychiatry, UMDNJ

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Official site of the Division of Child and Adolescent Psychiatry

Publications

• Aman M, Smgh N, Stewart A, Field C. The aberrant behavior checklist: a behavior rating scale for the assessment of treatment effects.Am J Ment Defic, 1985a;89(5):485 491 Campbell M, et al, Neuroleptic related dyskinesias in autistic children: a prospective longitudinal study, J Am Acad Child Adolesc Psychiatry 1997; 36(6): 835 43. Fomboime E. The epidemiology of autism: a review. Psychological Medicine, 1999; 29:769 786. Guy W. ECDEU assessment manual for psychopharmacology. Revised. NTMH Publication DHEW Publ No (adm.) 76 388. Bethesda, MD: National Institute of Mental Health, 1976; 217 222. McDougle CJ, Holmes JP, Bronson MR, Anderson GM, Volkmar FR, Price LH, Cohen DJ. Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open label study. J Am Acad Child Adolesc Psychiatry. 1997 May;36(5):685 93. Stahl SM. Dopamine system stabilizers, aripiprazole, and the next generation of antipsychotics, J Clin Psychiatry. 2001;62(l1).

• Responsible Party: Sherie Novotny, M.D., Assistant Professor, Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT00468130
• Other Study ID Numbers: 0220055441
• First Posted: May 2, 2007
• Last Update Posted: Jan 14, 2022
• Last Verified: Dec 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Sherie Novotny, M.D., Assistant Professor, Rutgers, The State University of New Jersey: Aggression; Irritability; Global autism severity
• Additional relevant MeSH terms: Aggression; Autistic Disorder; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Aripiprazole	Placebo
Arm/Group Description	Subjects in the experimental group will receive Aripiprazole Aripiprazole: Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects	Subjects in the control group will receive sugar pill Placebos: Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects
Period Title: Overall Study
STARTED	7	6
COMPLETED	5	4
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Aripiprazole	Placebo	Total
Arm/Group Description	Subjects in the experimental group will receive Aripiprazole Aripiprazole: Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects	Subjects in the control group will receive sugar pill Placebos: Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects	Total of all reporting groups
Overall Participants	7	6	13
Age (Count of Participants)
<=18 years	7 100%	6 100%	13 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.3 (2)	12.6 (2)	12.4 (2)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	1 16.7%	2 15.4%
Male	6 85.7%	5 83.3%	11 84.6%
Region of Enrollment (participants) [Number]
United States	7 100%	6 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Global Impression Improvement (CGI-AD)
Description	Clinical Global Impression Improvement (CGI)-AD (Guy, 1976). This is a standard rating scale with 7-point global severity and change scales which has been modified for Autistic Disorder. A rating of 2 is given when there is a substantial reduction in symptoms so that a treating clinician would be unlikely to change treatment. A rating of 1 is reserved for patients who become virtually symptom-free. A rating of 3 (minimally improved) on the CGI is defined as slight symptomatic improvement that is not deemed clinically significant. Administration time is approximately 2 minutes. Minimum is 1 and maximum is 5. A lower score indicates improvement, whereas a higher score indicates worsening.
Time Frame	Administered weekly, initial and week 8 reported

Outcome Measure Data

Analysis Population Description

Participants were children with autism who enrolled in the study.

Arm/Group Title	Aripiprazole	Placebo
Arm/Group Description	Subjects in the experimental group will receive Aripiprazole Aripiprazole: Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects	Subjects in the control group will receive sugar pill Placebos: Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects
Measure Participants	7	6
Initial CGI score	3.83 (0.41)	4.25 (1.25)
Week 8 CGI score	2.67 (1.21)	4.25 (1.5)

2. Secondary Outcome

Title	Aberrant Behavior Checklist
Description	Aberrant Behavior Checklist (ABC) (irritability section) (Aman et al, 1985). The Aberrant Behavior Checklist assesses drug and other treatment effects on mentally retarded individuals. It consists of a five-factor scale comprising 58 items. We will use the Irritability section to assess aggressive and agitated behavior. While the internal consistency, validity and test-retest reliability were reported to be very good, inter-rater reliability was moderate (Aman et al, 1985). The ABC will be filled out by an informant, and then reviewed by the psychiatrist. Administration time is approximately 10 minutes. Maximum is 36, minimum is 0, a lower score indicates improvement.
Time Frame	Administered biweekly, initial and week 8 reported

Outcome Measure Data

Analysis Population Description

Participants were children with autism who enrolled in the study.

Arm/Group Title	Aripiprazole	Placebo
Arm/Group Description	Participants in the clinical trial who were given aripiprazole	Participants in the clinical trial who were given placebo
Measure Participants	7	6
Initial, Irritability	15.67 (11.65)	8.00 (4.58)
Week 8, Irritability	6.83 (6.7)	8.67 (10.69)

Adverse Events

Time Frame	Adverse event data were collected during the period of the active study. Adverse events for each participant were collected during that participants enrollment in the study, initial contact through end of study, an average of 12 weeks for each participant.
Adverse Event Reporting Description	One subject withdrew due to a worsening of his depression after discontinuing his antidepressant medication, after being randomized.
Arm/Group Title	Aripiprazole		Placebo
Arm/Group Description	Subjects in the experimental group will receive Aripiprazole Aripiprazole: Subjects under 40 kg will be started on 2.5mg per day of aripiprazole for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects		Subjects in the control group will receive sugar pill Placebos: Inactive tablet made to resemble active tablet Subjects under 40 kg will be started on 2.5mg per day of placebo for the first week and increased to 5 mg at week 2. If clinically indicated (partial improvement with minimal or no side effects), the dosage will be increased each week by 2.5 mg until they reach a maximum of 10 mg at week 4. Medication will not be increased after week four but may be lowered in the case of adverse effects. Subjects over 40 kg will start at 5 mg and be increased to 10 mg at week 2. If clinically indicated, they will be increased each week by 5 mg until they reach a maximum of 20 mg at week 4. After week 4, the subject will remain on the same stable dose, unless the dose needs to be decreased due to adverse effects
All Cause Mortality
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)
Serious Adverse Events
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Aripiprazole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)		0/6 (0%)
Nervous system disorders
Worsening of depression	1/7 (14.3%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.