AutismPhase 2/3PGNCT00584701
Pharmacogenomics in Autism Treatment
A Phase 2/3 study testing Risperidone in people with Autism, run by University of California, San Francisco at 1 site in United States.
Trial summary
Autism is a complex neurodevelopmental disorder that is thought to involve an interaction between multiple and variable susceptibility genes, environmental factors, and epigenetic effects. Great concern has been raised about the marked increase in the prevalence of autism spectrum disorders in the last decade. Read more about this study
- Who is it for?
- Ages 4 to 18 years
- Conditions the study is for
- Autism
- What is being tested?
- Risperidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to May 2009
- Phase
- Phase 2/3
- 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 4 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Willingness to participate and written informed consent obtained from parent and when indicated by subject
- Confirmed DSM-IV-TR diagnosis of Autistic Disorder or Asperger's Disorder using the ADOS and the ADI-R, the current gold standards for diagnosing autism spectrum disorders, subject history, and clinical consensus with PI. The ADI-R and ADOS will be administered by research-reliable clinicians, including a clinical psychologist, a certified trainer on the ADOS and the ADI-R
- rated by study clinician as at least "moderate" on the CGI-Severity scale (a rating of ≥ 4) and greater than 18 on the ABC Irritability subscale
- Males or females of any race between 4 and 18 years of age (5) A nonverbal IQ greater than or equal to 55 on the Stanford-Binet:V (6) Women of childbearing potential must use an adequate method of contraception throughout the study.
Who cannot join
- Primary diagnosis of bipolar disorder, schizophrenia, or autism spectrum disorder other than Autistic and Asperger's Disorders
- Nonverbal IQ lower than 55 (Stanford-Binet:V)
- History of seizure activity in the past year (active seizures might confuse efficacy ratings)
- fever, infection, metabolic disturbance or any severe medical illness in the past year
- typical or atypical antipsychotic use within 8 weeks of study entry
- Inability of parents or care takers to give informed consent, travel to the visits, administer medication, or arrange for completion of rating scales. Other non-antipsychotic medications and non-pharmacological treatments will be allowed if started at least 2 months prior to the initial screening and must remain constant for the 8 weeks of this study. These treatments will be recorded as will a history of past trials of medications. Prohibiting ongoing treatment would be difficult to justify to parents and to the IRB and would make adequate recruitment for this pilot study difficult.
Trial locations and contacts
1 site in 1 country.
About this study
Autism is a complex neurodevelopmental disorder that is thought to involve an interaction between multiple and variable susceptibility genes, environmental factors, and epigenetic effects. Great concern has been raised about the marked increase in the prevalence of autism spectrum disorders in the last decade. Risperidone, the most studied atypical antipsychotic used in children, has been shown to improve severe behavioral difficulties in over half of children with autism who have these difficulties. However, not all children with autism and severe behavioral problems respond to risperidone, and for a few, it has significant side effects.
Two controlled studies and numerous open-label and long term studies in children with autism spectrum disorders using the atypical antipsychotic risperidone show a significant decrease of associated serious behavioral problems. The use of atypical antipsychotics is of great concern, however, because of their significant side effects and the fact that only two-thirds of children positively respond. Ways to predict response, appropriate dosage and serious side effects are needed.
Read the detailed description
For this study, we will identify 40 children (4 to 18 years old) with autism who also have serious behavioral problems. We will then treat them with risperidone. Blood samples will be obtained prior to treatment and at eight weeks of treatment or study exit. At that time, efficacy will be assessed using the Clinical Global Impression-Improvement scale (CGI-I) and the Irritability subscale of the Aberrant Behavior Checklist (ABC). Blood genomic profiles before and after risperidone treatment will be determined using Affymetrix oligonucleotide microarrays combined with RT-PCR.
Blood genomic profiles are shown to predict medication response for disorders such as cancer and epilepsy. This exploratory or discovery study will use blood genomic profiles before and after risperidone treatment in children with autism and severe behavioral difficulties to determine if the profiles can predict response to treatment. The ultimate goal of this line of research is to develop methods to predict which medications work for which child before initiating treatment, to predict which child might develop particular side effects, and to identify new treatment targets for future medication development.
Risperidone will be started at 0.5 mg at bedtime for 4 days and, if the current dosage is tolerated as evidenced by no more than mild sedation, no EPS or other moderate to severe AEs, and if there are continued behavioral symptoms, the dose will be increased to 1 mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5 mg will be added in the AM for a daily total of 1.5 mg. After that, dosages may be increased if there does not appear to be an adequate clinical response. Dosage will not be increased if there are side effects (e.g. excessive sedation, salivation, EPS, lactation) and may be decreased if it is not tolerated. If the investigator determines that a significant adverse reaction occurs or if the subject or his or her family wants to stop the study, the medication will be tapered or stopped depending on the dose and reason for stopping and the subject will be offered alternative treatment at the M.I.N.D. Institute Clinic or referred elsewhere. This dosing schedule mirrors that used in the two recent positive trials of risperidone for treating severe behavioral problems in autism (McCracken et al., 2002; Shea et al., 2004).
- Conditions
- Autism
- Being tested
- Risperidone
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RisperidoneDrug
Also called Risperdal
Dose will start at 0.5 mg and may be increased throughout the course of the study if no adverse events occur
| Study group | Role | What they receive |
|---|---|---|
| Risperidone | Experimental | Risperidone was started at 0.5mg at bedtime for 4 days. If that dosage was tolerated and there were continued behavioral symptoms, the dose was increased to 1mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5mg was added in the morning for a daily total of 1.5 mg. Receives: Drug: Risperidone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change of ABC - Irritability Subscale Score
Aberrant Behavior Checklist-Irritability (ABC-I)subscale: measure of assessing changes in symptoms of irritability in children with autism (survey that was normed on a developmentally delayed population of children and adults and is usually completed by a parent or caregiver. There are 45 items that are rated on a 4-point scale from "no problem" to "major problem." ABC-I scores ranges from 0 (best) to 45 (worst). A negative change signifies improvement.
We measured percent change of ABC-I scores from 8 weeks after risperidone treatment compared to baseline.
Measured: Baseline, 8 weeks
Secondary outcomes (1)
Exon Expression Positively or Negatively Correlated With Percentage Improvement in ABC-I
Affymetrix GeneChip Human Exon 1.0 ST Arrays (Affymetrix, Santa Clara, CA, USA) were used to obtain gene expression values. Raw data (Affymetrix.CEL files) was imported into Partek Genomics Suite 6.4 (Partek, St Louis, MO, USA). Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization.
Exons in genes correlated with percentage improvement on the Aberrant Behavior Checklist Irritability subscale were identified.
Measured: Baseline, 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2008 (estimated)
- Study startJan 2008
- Primary completionMay 2009
- Study completionMay 2009
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 AutismStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP, National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Robert L Hendren, DO, Principal investigator, UC San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00584701
- Sponsor's protocol ID
- 200715817-1
- Other IDs
- R21MH080026
- Acronym
- PG
- Status last verified
- Jun 2012
- First submitted
- 22 Dec 2007
- Last updated
- 24 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenomics in Autism Treatment
- ClinicalTrials.gov ID
- NCT00584701
- Acronym / sponsor ID
- PG / 200715817-1
- Conditions
- Autism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Janssen, LP, National Institute of Mental Health (NIMH)
- Study start
- Jan 2008
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 2 Jan 2008 (estimated)
- Results
- Posted 24 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Autism is a complex neurodevelopmental disorder that is thought to involve an interaction between multiple and variable susceptibility genes, environmental factors, and epigenetic effects. Great concern has been raised about the marked increase in the prevalence of autism spectrum disorders in the last decade. Risperidone, the most studied atypical antipsychotic used in children, has been shown to improve severe behavioral difficulties in over half of children with autism who have these difficulties. However, not all children with autism and severe behavioral problems respond to risperidone, and for a few, it has significant side effects.
Two controlled studies and numerous open-label and long term studies in children with autism spectrum disorders using the atypical antipsychotic risperidone show a significant decrease of associated serious behavioral problems. The use of atypical antipsychotics is of great concern, however, because of their significant side effects and the fact that only two-thirds of children positively respond. Ways to predict response, appropriate dosage and serious side effects are needed.
Detailed description
For this study, we will identify 40 children (4 to 18 years old) with autism who also have serious behavioral problems. We will then treat them with risperidone. Blood samples will be obtained prior to treatment and at eight weeks of treatment or study exit. At that time, efficacy will be assessed using the Clinical Global Impression-Improvement scale (CGI-I) and the Irritability subscale of the Aberrant Behavior Checklist (ABC). Blood genomic profiles before and after risperidone treatment will be determined using Affymetrix oligonucleotide microarrays combined with RT-PCR.
Blood genomic profiles are shown to predict medication response for disorders such as cancer and epilepsy. This exploratory or discovery study will use blood genomic profiles before and after risperidone treatment in children with autism and severe behavioral difficulties to determine if the profiles can predict response to treatment. The ultimate goal of this line of research is to develop methods to predict which medications work for which child before initiating treatment, to predict which child might develop particular side effects, and to identify new treatment targets for future medication development.
Risperidone will be started at 0.5 mg at bedtime for 4 days and, if the current dosage is tolerated as evidenced by no more than mild sedation, no EPS or other moderate to severe AEs, and if there are continued behavioral symptoms, the dose will be increased to 1 mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5 mg will be added in the AM for a daily total of 1.5 mg. After that, dosages may be increased if there does not appear to be an adequate clinical response. Dosage will not be increased if there are side effects (e.g. excessive sedation, salivation, EPS, lactation) and may be decreased if it is not tolerated. If the investigator determines that a significant adverse reaction occurs or if the subject or his or her family wants to stop the study, the medication will be tapered or stopped depending on the dose and reason for stopping and the subject will be offered alternative treatment at the M.I.N.D. Institute Clinic or referred elsewhere. This dosing schedule mirrors that used in the two recent positive trials of risperidone for treating severe behavioral problems in autism (McCracken et al., 2002; Shea et al., 2004).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Risperidone | Experimental | Drug: RisperidoneRisperidone was started at 0.5mg at bedtime for 4 days. If that dosage was tolerated and there were continued behavioral symptoms, the dose was increased to 1mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5mg was added in the morning for a daily total of 1.5 mg. |
Who may qualify
- Ages
- 4 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Willingness to participate and written informed consent obtained from parent and when indicated by subject
- Confirmed DSM-IV-TR diagnosis of Autistic Disorder or Asperger's Disorder using the ADOS and the ADI-R, the current gold standards for diagnosing autism spectrum disorders, subject history, and clinical consensus with PI. The ADI-R and ADOS will be administered by research-reliable clinicians, including a clinical psychologist, a certified trainer on the ADOS and the ADI-R
- rated by study clinician as at least "moderate" on the CGI-Severity scale (a rating of ≥ 4) and greater than 18 on the ABC Irritability subscale
- Males or females of any race between 4 and 18 years of age (5) A nonverbal IQ greater than or equal to 55 on the Stanford-Binet:V (6) Women of childbearing potential must use an adequate method of contraception throughout the study.
Key exclusion criteria (6 listed)
- Primary diagnosis of bipolar disorder, schizophrenia, or autism spectrum disorder other than Autistic and Asperger's Disorders
- Nonverbal IQ lower than 55 (Stanford-Binet:V)
- History of seizure activity in the past year (active seizures might confuse efficacy ratings)
- fever, infection, metabolic disturbance or any severe medical illness in the past year
- typical or atypical antipsychotic use within 8 weeks of study entry
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 |
|---|---|---|
| RisperidoneAlso: RisperdalDose will start at 0.5 mg and may be increased throughout the course of the study if no adverse events occur | Drug | Risperidone |
Primary outcome
Percent Change of ABC - Irritability Subscale Score
Time frame: Baseline, 8 weeks
Aberrant Behavior Checklist-Irritability (ABC-I)subscale: measure of assessing changes in symptoms of irritability in children with autism (survey that was normed on a developmentally delayed population of children and adults and is usually completed by a parent or caregiver. There are 45 items that are rated on a 4-point scale from "no problem" to "major problem." ABC-I scores ranges from 0 (best) to 45 (worst). A negative change signifies improvement. We measured percent change of ABC-I scores from 8 weeks after risperidone treatment compared to baseline.
1 secondary outcome
Exon Expression Positively or Negatively Correlated With Percentage Improvement in ABC-I
Time frame: Baseline, 8 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2012.
- 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.
Robert L Hendren, DO principal investigator
UC San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Risperidone in people with Autism, run by University of California, San Francisco 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 4 inclusion and 6 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 24 Jul 2012. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 24 Jul 2012). 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?
Percent Change of ABC - Irritability Subscale Score (time frame: Baseline, 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 24 Jul 2012.