Risperidone Treatment In Children With Autism Spectrum Disorder And High Levels Of Repetitive Behavior (ProjectV)

Risperidone Treatment In Children With Autism Spectrum Disorder And High Levels of Repetitive Behavior

The proposed study attempts to deepen our understanding of repetitive behaviors in autism spectrum disorders (ASD) and its treatment by examining the changes in key neural circuits associated with risperidone treatment using functional MRI. This study is a substudy of a larger center grant (IRB#07-03-066). Other studies also under this center grant, include: IRB#03-02-085, IRB#95-01-028. All participants will have the option to enter another sub-study, should they meet criteria. The proposed study will address this aim by mounting a controlled trial of 52 children with Autism Spectrum Disorder. After screening assessment, children will enter a three-part study. Phase 1 will be an 8-week, double-blind, placebo-controlled flexible dose trial of risperidone. The extension phase is a 16-week open-label maintenance phase for responders to risperidone or placebo. Non-responders to placebo will be invited to enroll in the eight-week open-label study. 48 of the participants will also undergo fMRI at Week 8 while on blinded treatment, as an optional sub-study. The medication will be dispensed in a liquid suspension and the dose will range from 0.5 mg to 4.0mg.

Study Overview

• Status: Completed
• Conditions: Autism
• Intervention / Treatment: Drug: Risperidone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or females of any race or ethnicity between the ages of 8 and 16 years,
2. Body weight greater than 20 kg body weight
3. DSM-IV diagnosis of Autistic Disorder, PDD, NOS, or Asperger's Disorder (established by clinical assessment, corroborated by standard cutoff scores on the Autism Diagnostic Interview and Autism Diagnostic Observation Schedule), as determined by ADI-R administered by raters who are trained to research reliability, and confirmed by an experienced and reliable clinician using DSM-IV-TR criteria.
4. Anticonvulsants used for the treatment of a seizure disorder will be permitted if the dosage has been stable for 4 weeks and the patient is seizure free for at least 6 months,
5. Clinical Global Impression (CGI) Severity score of at least 4; and subjects must also have a score greater than 7 on the first 3 items of the Compulsions Subscale of the Revised PDD CY-BOCS.
6. Ambulatory status (outpatient or day-treatment) at time of randomization
7. Subject must demonstrate a mental age >18 months as determined by the Vineland Adaptive Behavior Scales.
8. Subjects must be free neuroleptics two weeks prior to baseline. Subjects who are on SSRIs or stimulants, must be on a stable dose for at least 4 weeks prior to baseline visit.
9. Subjects and their parents (guardians) must be judged reliable for medication compliance and must agree to keep appointments for study visits and tests as outlined in the protocol.

Exclusion Criteria:

1. IQ below mental age of 18 months as measured by either the age-appropriate form of the Wechsler, the Revised Leiter, or the Mullen
2. Females with a positive Beta HCG pregnancy test,
3. Evidence of a prior adequate trial with risperidone (defined as duration of four weeks or more at a dose of at least 2 mg per day)
4. Evidence of hypersensitivity to risperidone (defined as allergic response [e.g., skin rash]) or potentially serious adverse effect (e.g., significant tachycardia)
5. Past history of neuroleptic malignant syndrome.
6. DSM-IV diagnosis of substance abuse.
7. A significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder identified by history, physical examination or laboratory tests.
8. The use of any other psychotropic medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Children get randomized to either placebo or risperidone; Other Names: Inactive medicine
Active Comparator: Open-Label Risperidone; Risperidone oral solution (1mg/mL) qd for 8 weeks.	Drug: Risperidone; children get randomized to either placebo or active risperidone; Other Names: Risperdal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Aberrant Behavior Checklist	5 years

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: James McCracken, MD, University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2008
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: July 28, 2010
• First Submitted That Met QC Criteria: July 28, 2010
• First Posted (Estimate): July 29, 2010

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Repetitive Behaviors; ages 8-16
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autistic Disorder; Autism Spectrum Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: 07-06-033; P50HD055784 (U.S. NIH Grant/Contract)