Pervasive Developmental DisorderPhase 3NCT00870727
Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
A Phase 3 study testing Aripiprazole oral product in people with Pervasive Developmental Disorder, run by Indiana University at 1 site in United States.
Trial summary
The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Pervasive Developmental Disorder
- What is being tested?
- Aripiprazole oral product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to May 2015
- Phase
- Phase 3
- 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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight.
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS).
- Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG).
- Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale.
- Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50.
Who cannot join
- DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months.
- Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis).
- A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing.
- Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered.
- Females with a positive urine pregnancy test.
- Evidence of a prior adequate trial of aripiprazole (defined as equal to or greater than 2 weeks at equal to or greater than 5 mg per day. When there is not evidence of a prior adequate trial, subjects must be medication-free for a least 2 weeks prior to baseline.
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- History of neuroleptic malignant syndrome.
- Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study for any reason.
- Hypersensitivity to aripiprazole [e.g., allergic response or serious adverse effect] (significant tachycardia).
Trial locations and contacts
1 site in 1 country.
United States1 site
Riley Hospital for Children, Christian Sarkine Autism Treatment Center
Indianapolis, Indiana, 46202
About this study
Official title: Pharmacotherapy of Pervasive Developmental Disorders
The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. The investigators hypothesize that aripiprazole will be more effective than placebo for reducing aggression, tantrum and self-injurious behavior in children with Pervasive Developmental Disorder.
Read the detailed description
Pervasive developmental disorders (PDDs) are characterized by severe impairments in social interaction and communication in addition to restricted patterns of interests and activities. Research suggests that a dysregulation of the dopamine and serotonin systems contributes to these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics were reported in subjects with PDD, research shifted to the atypical antipsychotics which have been shown to be better tolerated and effective in this population. However, the atypical antipsychotics have also been associated with adverse effects. Thus there remains a need for a novel pharmacotherapy that would be safe and effective for children and adolescents with PDDs. The primary objectives of this study are to determine whether aripiprazole is effective and well tolerated for irritability in children and adolescents with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation phase.
- Conditions
- Pervasive Developmental Disorder
- Being tested
- Aripiprazole oral product, Placebo oral capsule
- Keywords
- PDD NOS
- Medical subject headings
- Child Development Disorders, Pervasive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aripiprazole oral productDrug
Also called Abilify
Minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment.
Placebo oral capsuleDrug
Also called Sugar pill
Placebo will be identical in size and appearance to study drug.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1. Aripiprazole oral product | Experimental | Participants will receive Aripiprazole oral product with a minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment. Receives: Drug: Aripiprazole oral product |
| Arm 2. Placebo oral capsule | Placebo comparator | Participants will receive matching (identical in size and appearance to study drug) placebo oral capsules over 8-weeks of treatment. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Four participants assigned to placebo completed an exit interview prior to week 8. One participant assigned to placebo and one participant assigned to aripiprazole withdrew from the study without completing an exit interview.
Measured: Double-blind phase study exit - up to 8 weeks
Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Irritability subscale is 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.
Measured: Weeks 1, 2, 3, 4, 6 and 8
Secondary outcomes (4)
Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. The 16-item Hyperactivity subscale covers overactivity (7 items), impulsiveness (2 items), inattention (3 items) and noncompliance (4 items). It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores is 0 to 48 on the Hyperactivity subscale. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.
Measured: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Inappropriate Speech subscale is 0 to 12. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.
Measured: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item Parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Social Withdrawal subscale is 0 to 48. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.
Measured: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Stereotypy subscale is 0 to 21. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints.
Measured: Weeks 1, 2, 3, 4, 6 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2009 (estimated)
- Study startFeb 2009
- Primary completionMar 2015
- Study completionMay 2015
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 Pervasive Developmental DisorderStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kimberly A. Stigler, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00870727
- Sponsor's protocol ID
- 0805-26
- Other IDs
- MH 082119
- Status last verified
- Mar 2018
- First submitted
- 2 Feb 2009
- Last updated
- 2 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacotherapy of Pervasive Developmental Disorders
- ClinicalTrials.gov ID
- NCT00870727
- Acronym / sponsor ID
- 0805-26
- Conditions
- Pervasive Developmental Disorder
- Keywords
- PDD NOS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), Bristol-Myers Squibb
- Study start
- Feb 2009
- Primary completion
- Mar 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 27 Mar 2009 (estimated)
- Results
- Posted 28 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. The investigators hypothesize that aripiprazole will be more effective than placebo for reducing aggression, tantrum and self-injurious behavior in children with Pervasive Developmental Disorder.
Detailed description
Pervasive developmental disorders (PDDs) are characterized by severe impairments in social interaction and communication in addition to restricted patterns of interests and activities. Research suggests that a dysregulation of the dopamine and serotonin systems contributes to these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics were reported in subjects with PDD, research shifted to the atypical antipsychotics which have been shown to be better tolerated and effective in this population. However, the atypical antipsychotics have also been associated with adverse effects. Thus there remains a need for a novel pharmacotherapy that would be safe and effective for children and adolescents with PDDs. The primary objectives of this study are to determine whether aripiprazole is effective and well tolerated for irritability in children and adolescents with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1. Aripiprazole oral product | Experimental | Drug: Aripiprazole oral productParticipants will receive Aripiprazole oral product with a minimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment. |
| Arm 2. Placebo oral capsule | Placebo comparator | Drug: Placebo oral capsuleParticipants will receive matching (identical in size and appearance to study drug) placebo oral capsules over 8-weeks of treatment. |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight.
- Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS).
- Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG).
- Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale.
- Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50.
Key exclusion criteria (9 listed)
- DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months.
- Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis).
- A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing.
- Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered.
- Females with a positive urine pregnancy test.
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 |
|---|---|---|
| Aripiprazole oral productAlso: AbilifyMinimum dose of 2 mg per day to a maximum dose of 20 mg per day over 8-weeks of treatment. | Drug | Arm 1. Aripiprazole oral product |
| Placebo oral capsuleAlso: Sugar pillPlacebo will be identical in size and appearance to study drug. | Drug | Arm 2. Placebo oral capsule |
Primary outcome
Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
Time frame: Double-blind phase study exit - up to 8 weeks
Clinical Global Impressions (Guy, 1976) global improvement (CGI-I) is designed to take into account all factors to arrive at an assessment of response to treatment. The CGI-I scale ranges from 1 to 7, with lower scores indicating greater improvement (1=very much improved and 2=much improved). Participants with a CGI-I score of 1 or 2 were classified as improved. Four participants assigned to placebo completed an exit interview prior to week 8. One participant assigned to placebo and one participant assigned to aripiprazole withdrew from the study without completing an exit interview.
Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase
Time frame: Weeks 1, 2, 3, 4, 6 and 8
The Aberrant Behavior Checklist (ABC) is a symptom checklist for assessing problem behaviors in individuals ages 6 to 54 years-old with mental retardation. The full ABC is a 58-item parent rating with five factors: Irritability, Social Withdrawal, Stereotypy, Hyperactivity and Inappropriate Speech. It has been used as a primary outcome measure in several trials in children with developmental disabilities. The interpretation of the tool and its subscales is that a greater number of items indicates greater severity. The range of scores for the Irritability subscale is 0 to 45. Means were estimated using a repeated measures linear regression model with treatment group, baseline score, study week (in categories), and Tanner stage as covariates. A linear contrast estimated the average across study timepoints. Confidence intervals reflect a Bonferroni multiple testing correction accounting for the selection of two primary outcomes.
4 secondary outcomes
Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase
Time frame: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase
Time frame: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase
Time frame: Weeks 1, 2, 3, 4, 6 and 8
Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase
Time frame: Weeks 1, 2, 3, 4, 6 and 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Kimberly A. Stigler, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aripiprazole oral product in people with Pervasive Developmental Disorder, run by Indiana University 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 5 inclusion and 9 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 2 Jan 2019. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 28 Nov 2018). 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 Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2) (time frame: Double-blind phase study exit - up to 8 weeks). The study lists 2 primary outcomes in all. 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 2 Jan 2019.