Autism
Conditions
Keywords
Aggression, Irritability, Global autism severity
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.
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.
Interventions
DRUGAripiprazole
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
DRUGPlacebos
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
Sponsors
University of Medicine and Dentistry of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aripiprazole 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 | 7 |
| Placebo 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 | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Aripiprazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 7 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 12.6 years STANDARD_DEVIATION 2 | 12.3 years STANDARD_DEVIATION 2 | 12.4 years STANDARD_DEVIATION 2 |
| Region of Enrollment United States | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 1 / 7 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
Clinical Global Impression Improvement (CGI-AD)
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
Population: Participants were children with autism who enrolled in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole | Clinical Global Impression Improvement (CGI-AD) | Initial CGI score | 3.83 score on a scale | Standard Deviation 0.41 |
| Aripiprazole | Clinical Global Impression Improvement (CGI-AD) | Week 8 CGI score | 2.67 score on a scale | Standard Deviation 1.21 |
| Placebo | Clinical Global Impression Improvement (CGI-AD) | Initial CGI score | 4.25 score on a scale | Standard Deviation 1.25 |
| Placebo | Clinical Global Impression Improvement (CGI-AD) | Week 8 CGI score | 4.25 score on a scale | Standard Deviation 1.5 |
Secondary
Aberrant Behavior Checklist
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
Population: Participants were children with autism who enrolled in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aripiprazole | Aberrant Behavior Checklist | Initial, Irritability | 15.67 score on a scale | Standard Deviation 11.65 |
| Aripiprazole | Aberrant Behavior Checklist | Week 8, Irritability | 6.83 score on a scale | Standard Deviation 6.7 |
| Placebo | Aberrant Behavior Checklist | Initial, Irritability | 8.00 score on a scale | Standard Deviation 4.58 |
| Placebo | Aberrant Behavior Checklist | Week 8, Irritability | 8.67 score on a scale | Standard Deviation 10.69 |