Autistic DisorderPhase 3NCT00005014
Treatment of Autism in Children and Adolescents
A Phase 3 study testing Risperidone in people with Autistic Disorder, run by National Institute of Mental Health (NIMH) at 5 sites in United States.
Trial summary
This study is designed to determine the effectiveness of risperidone, a drug treatment for the interfering symptoms of Autistic Disorder in children and adolescents between the ages of 5 and 17. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Autistic Disorder
- What is being tested?
- Risperidone
- How many people
- 101 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 1997to Feb 2001
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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
- Males and females between the ages of 5 and 17 years 2 months.
- Weight of 15 kg or greater.
- DSM-IV diagnosis of Autistic Disorder.
- Inpatient or outpatient.
- Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
- Anticonvulsants used for treatment of seizure disorder permitted if the dosage has been stable for 4 weeks and patient seizure free for at least 6 months.
Show all 9Show fewer
- Clinical Global Impression Severity score of at least 4 and a)18 or greater on the Irritability Scale of the Aberrant Behavior Checklist or b) .5 total score on the Ritvo-Freeman scale.
- Mental age of at least 18 months.
- Negative pregnancy test
Who cannot join
- IQ below 18 months.
- Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
- Evidence of hypersensitivity to risperidone.
- Past history of neuroleptic malignant syndrome.
- DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
- Significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder.
- Weight less than 15 kg.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Kennedy Krieger Institute
Baltimore, Maryland, 21231
Ohio State Univ
Columbus, Ohio, 43210
Indiana Univ / Riley Hosp for Children
Indianapolis, Indiana, 46202
UCLA
Los Angeles, California, 90024
Yale Univ
New Haven, Connecticut, 06520
About this study
Official title: Placebo-Controlled Study of Risperidone for the Treatment of Children and Adolescents With Autism and Negative Behavioral Symptoms
This study is designed to determine the effectiveness of risperidone, a drug treatment for the interfering symptoms of Autistic Disorder in children and adolescents between the ages of 5 and 17. Between 100 and 120 patients will be participating in this research study at five academic medical centers in the United States. The primary aim of the treatment is to reduce impairing behavioral symptoms such as aggression, explosive outbursts, or self-injurious behavior, without significant side effects. A secondary aim is to evaluate possible improvement in the level of social relatedness, attention, motor coordination, and short-term memory.
This study is a placebo-controlled, double-blind study (neither the investigators nor patients know if the treatment being given is risperidone or an inactive substance, placebo). Patients will be asked to participate for 6 to 8 months. For the first 8 weeks, patients will receive either risperidone or placebo, randomly chosen. At the end of the 8 weeks, those patients who have improved and were on risperidone will be asked to continue on this medication for another 4 months. The last two months of the study are again double-blind (neither patients nor investigators know treatment). Patients will either continue risperidone treatment or be gradually tapered from risperidone (placebo-substitution). This blinded discontinuation phase will last 2 months during which patients will be closely monitored for recurrence or worsening of symptoms. Patients who have been treated with placebo in the first 8 weeks of the study and have not improved will be treated with risperidone. Weekly visits are required for the first 8 weeks of the study, monthly visits for the following 4 months, and weekly visits during the last 2 months of the study.
Read the detailed description
The primary purpose of this study is to compare the relative safety and efficacy of risperidone and placebo in the treatment of children and adolescents with autistic disorder.
HYPOTHESES: (1) Risperidone will be more effective than placebo in reducing impulsive aggression, agitation, self-injurious behavior, and troublesome repetitive behavior associated with autism. (2) Risperidone will result in more sedation (transient) and weight gain than placebo. (3) Patients continued on risperidone will be significantly less likely to experience exacerbation of symptoms of irritability, aggression, agitation, and stereotypy than those randomized to placebo, as measured by the Aberrant Behavior Checklist (ABC), the Ritvo-Freeman Real Life Rating Scale, and the compulsions scale from the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). (4) Patients continued on risperidone would show superior adjustment and functioning at the end of the trial, as evidenced by lower Clinical Global Impression ratings, when compared to patients randomized to placebo.
Design Phase I: Double-Blind Phase - Randomized, double-blind, placebo-controlled, parallel groups design. Eight-week double-blind treatment with risperidone or placebo. Eight-week open trial with risperidone for placebo non-responders (patients who were randomized to placebo and showed no improvement).
(Risperidone responders will be eligible to enter the four-month extension study. Placebo responders and risperidone non-responders will be managed as clinically appropriate by each research site.) Phase II: Extension Study - Four-month, open treatment with risperidone. Dose adjustment permitted according to clinical assessment (efficacy or adverse events). Two-month, randomized, double-blind, placebo-controlled discontinuation, parallel group design.
Completers of four-month Extension Phase protocol who have maintained significantly improved status (decrease greater than 25% in ABC from Protocol I Baseline ratings and CGI of much or very much improved) will be randomized at the end of four months to placebo substitution or risperidone continuation. Group assigned to placebo substitution will undergo weekly blinded reductions of entry dose (dosage at end of Phase I) by 25% per week over three consecutive weeks. After full placebo substitution, placebo group will remain on placebo for total of up to 5 weeks (three-week taper, five-week remaining on placebo). Group assigned to continued active treatment will be maintained on entry dose level for full 8 weeks of Phase II, assuming no behavioral deterioration. Active treatment patients may have dose reduced for treatment emergent effects.
Randomization - Balanced within site by Tanner Stage (pre-pubertal: Tanner I or II as measured by the absence of pubic hair; post-pubertal: Tanner III or greater), gender, and anticonvulsant use.
- Conditions
- Autistic Disorder
- Being tested
- Risperidone
- Keywords
- Autistic Disorder, 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2000 (estimated)
- Study startOct 1997
- Study completionFeb 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Autistic DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Masking
- Double blind
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Michael Aman, Principal investigator, Ohio State UnivJames McCracken, Principal investigator, University of California, Los AngelesChristopher J McDougle, Principal investigator, Indiana Univ / Riley Hosp for ChildrenElaine Tierney, Principal investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.Fred Volkmar, Principal investigator, Yale UnivBenedetto Vitiello, NIMH Coordinator, Natl Institute of Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005014
- Sponsor's protocol ID
- N01 MH70001
- Other IDs
- N01 MH70009, N01 MH80011, N01 MH70010, N01 MH70001, DSIR CT
- Status last verified
- Aug 2010
- First submitted
- 31 Mar 2000
- Last updated
- 17 Apr 2014
- Results posted
- No
Publications
McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002 Aug 1;347(5):314-21. doi: 10.1056/NEJMoa013171.
PubMed 12151468Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ, Chuang S, Martin A, Shah B, Gonzalez NM, Swiezy NB, Ritz L, Koenig K, McGough J, Ghuman JK, Lindsay RL. Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol. 2005 Dec;15(6):869-84. doi: 10.1089/cap.2005.15.869.
PubMed 16379507Williams SK, Scahill L, Vitiello B, Aman MG, Arnold LE, McDougle CJ, McCracken JT, Tierney E, Ritz L, Posey DJ, Swiezy NB, Hollway J, Cronin P, Ghuman J, Wheeler C, Cicchetti D, Sparrow S. Risperidone and adaptive behavior in children with autism. J Am Acad Child Adolesc Psychiatry. 2006 Apr;45(4):431-9. doi: 10.1097/01.chi.0000196423.80717.32.
PubMed 16601648Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
PubMed 37811711Levine SZ, Kodesh A, Goldberg Y, Reichenberg A, Furukawa TA, Kolevzon A, Leucht S. Initial severity and efficacy of risperidone in autism: Results from the RUPP trial. Eur Psychiatry. 2016 Feb;32:16-20. doi: 10.1016/j.eurpsy.2015.11.004. Epub 2016 Jan 21.
PubMed 26802979
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled Study of Risperidone for the Treatment of Children and Adolescents With Autism and Negative Behavioral Symptoms
- ClinicalTrials.gov ID
- NCT00005014
- Acronym / sponsor ID
- N01 MH70001
- Conditions
- Autistic Disorder
- Keywords
- Autistic Disorder, Risperidone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Oct 1997
- Study completion
- Feb 2001
- First posted
- 3 Apr 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to determine the effectiveness of risperidone, a drug treatment for the interfering symptoms of Autistic Disorder in children and adolescents between the ages of 5 and 17. Between 100 and 120 patients will be participating in this research study at five academic medical centers in the United States. The primary aim of the treatment is to reduce impairing behavioral symptoms such as aggression, explosive outbursts, or self-injurious behavior, without significant side effects. A secondary aim is to evaluate possible improvement in the level of social relatedness, attention, motor coordination, and short-term memory.
This study is a placebo-controlled, double-blind study (neither the investigators nor patients know if the treatment being given is risperidone or an inactive substance, placebo). Patients will be asked to participate for 6 to 8 months. For the first 8 weeks, patients will receive either risperidone or placebo, randomly chosen. At the end of the 8 weeks, those patients who have improved and were on risperidone will be asked to continue on this medication for another 4 months. The last two months of the study are again double-blind (neither patients nor investigators know treatment). Patients will either continue risperidone treatment or be gradually tapered from risperidone (placebo-substitution). This blinded discontinuation phase will last 2 months during which patients will be closely monitored for recurrence or worsening of symptoms. Patients who have been treated with placebo in the first 8 weeks of the study and have not improved will be treated with risperidone. Weekly visits are required for the first 8 weeks of the study, monthly visits for the following 4 months, and weekly visits during the last 2 months of the study.
Detailed description
The primary purpose of this study is to compare the relative safety and efficacy of risperidone and placebo in the treatment of children and adolescents with autistic disorder.
HYPOTHESES: (1) Risperidone will be more effective than placebo in reducing impulsive aggression, agitation, self-injurious behavior, and troublesome repetitive behavior associated with autism. (2) Risperidone will result in more sedation (transient) and weight gain than placebo. (3) Patients continued on risperidone will be significantly less likely to experience exacerbation of symptoms of irritability, aggression, agitation, and stereotypy than those randomized to placebo, as measured by the Aberrant Behavior Checklist (ABC), the Ritvo-Freeman Real Life Rating Scale, and the compulsions scale from the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). (4) Patients continued on risperidone would show superior adjustment and functioning at the end of the trial, as evidenced by lower Clinical Global Impression ratings, when compared to patients randomized to placebo.
Design Phase I: Double-Blind Phase - Randomized, double-blind, placebo-controlled, parallel groups design. Eight-week double-blind treatment with risperidone or placebo. Eight-week open trial with risperidone for placebo non-responders (patients who were randomized to placebo and showed no improvement).
(Risperidone responders will be eligible to enter the four-month extension study. Placebo responders and risperidone non-responders will be managed as clinically appropriate by each research site.) Phase II: Extension Study - Four-month, open treatment with risperidone. Dose adjustment permitted according to clinical assessment (efficacy or adverse events). Two-month, randomized, double-blind, placebo-controlled discontinuation, parallel group design.
Completers of four-month Extension Phase protocol who have maintained significantly improved status (decrease greater than 25% in ABC from Protocol I Baseline ratings and CGI of much or very much improved) will be randomized at the end of four months to placebo substitution or risperidone continuation. Group assigned to placebo substitution will undergo weekly blinded reductions of entry dose (dosage at end of Phase I) by 25% per week over three consecutive weeks. After full placebo substitution, placebo group will remain on placebo for total of up to 5 weeks (three-week taper, five-week remaining on placebo). Group assigned to continued active treatment will be maintained on entry dose level for full 8 weeks of Phase II, assuming no behavioral deterioration. Active treatment patients may have dose reduced for treatment emergent effects.
Randomization - Balanced within site by Tanner Stage (pre-pubertal: Tanner I or II as measured by the absence of pubic hair; post-pubertal: Tanner III or greater), gender, and anticonvulsant use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Males and females between the ages of 5 and 17 years 2 months.
- Weight of 15 kg or greater.
- DSM-IV diagnosis of Autistic Disorder.
- Inpatient or outpatient.
- Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
Key exclusion criteria (7 listed)
- IQ below 18 months.
- Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
- Evidence of hypersensitivity to risperidone.
- Past history of neuroleptic malignant syndrome.
- DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
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 |
|---|---|---|
| Risperidone | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Background: PubMed 12151468McCracken JT, McGough J, Shah B, Cronin P, Hong D, Aman MG, Arnold LE, Lindsay R, Nash P, Hollway J, McDougle CJ, Posey D, Swiezy N, Kohn A, Scahill L, Martin A, Koenig K, Volkmar F, Carroll D, Lancor A, Tierney E, Ghuman J, Gonzalez NM, Grados M, Vitiello B, Ritz L, Davies M, Robinson J, McMahon D; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002 Aug 1;347(5):314-21. doi: 10.1056/NEJMoa013171.
- Background: PubMed 16379507Aman MG, Arnold LE, McDougle CJ, Vitiello B, Scahill L, Davies M, McCracken JT, Tierney E, Nash PL, Posey DJ, Chuang S, Martin A, Shah B, Gonzalez NM, Swiezy NB, Ritz L, Koenig K, McGough J, Ghuman JK, Lindsay RL. Acute and long-term safety and tolerability of risperidone in children with autism. J Child Adolesc Psychopharmacol. 2005 Dec;15(6):869-84. doi: 10.1089/cap.2005.15.869.
- Background: PubMed 16601648Williams SK, Scahill L, Vitiello B, Aman MG, Arnold LE, McDougle CJ, McCracken JT, Tierney E, Ritz L, Posey DJ, Swiezy NB, Hollway J, Cronin P, Ghuman J, Wheeler C, Cicchetti D, Sparrow S. Risperidone and adaptive behavior in children with autism. J Am Acad Child Adolesc Psychiatry. 2006 Apr;45(4):431-9. doi: 10.1097/01.chi.0000196423.80717.32.
- Derived from this study: PubMed 37811711Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.
- Derived from this study: PubMed 26802979Levine SZ, Kodesh A, Goldberg Y, Reichenberg A, Furukawa TA, Kolevzon A, Leucht S. Initial severity and efficacy of risperidone in autism: Results from the RUPP trial. Eur Psychiatry. 2016 Feb;32:16-20. doi: 10.1016/j.eurpsy.2015.11.004. Epub 2016 Jan 21.
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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.
Michael Aman principal investigator
Ohio State Univ
James McCracken principal investigator
University of California, Los Angeles
Christopher J McDougle principal investigator
Indiana Univ / Riley Hosp for Children
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Risperidone in people with Autistic Disorder, run by National Institute of Mental Health (NIMH) at 5 sites 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 9 inclusion and 7 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 17 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005014, which also lists 5 linked publications.
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 17 Apr 2014.