Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism

NCT00211757 | Completed Phase 2 Results

• 2 other identifiers: 01-02941R21NS043979
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The study is designed to assess the efficacy of treatment with divalproex sodium (DS) vs. placebo in childhood/adolescent autism fulfilling DSM-IV and Autism Diagnostic Interview (ADI) criteria. Currently, there are no FDA-approved treatments for this disorder, although behavioral and educational therapies and a variety of medications may play a role in the management of some autistic symptoms.

Conditions

Autism

Keywords

autism; aggression; irritability; divalproex sodium

Outcome Measures

Primary Outcomes (2)

• Number of Participants Reporting Improvement on the Clinical Global Impression

  The CGI-I is a 7-point improvement scale. Ratings of 1 or 2 (responders) indicate a substantial reduction in symptoms. A rating of 3 (minimally improved) on the CGI is defined as a slight symptomatic improvement that is not deemed clinically significant; patients with such an improvement were not considered responders. Two versions of this test were used, one focused on irritability (primary outcome measure) and a general version CGI-I-autism focused on all symptoms including core symptom domains. The CGI-I irritability took into consideration the scores from the ABC-Irritability subscale, the OAS-M aggression and irritability subscales and information from open-ended questioning related to the degree of interference, nature, and range of behavioral problems at school and at home

  Baseline to end of study (week 15)

• Change in Aberrant Behaviors as Measured by the Aberrant Behavior Checklist Scores

  The Aberrant Behavior Checklist is designed to objectively identify five behavior sub scales through observation by the primary caregiver: irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech. The ABC was filled out by parents on a scale from 0-3 for each category. (0 being not a problem, 3 being severe problem). Scores from all sub scales were added (scoring 0-45 for Irritability subscale, 0-48 for Lethargy subscale, 0-21 for stereotypy scale, 0-48 for hyperactivity sub-scale, and 0-12 for inappropriate speech sub-scale) to obtain an overall score with a an overall scoring range of 0-174. Higher scores were indicative of worsening symptoms.

  Baseline and End of Study (week 15)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.

Drug: Placebo

Divalproex Sodium

EXPERIMENTAL

Subjects will receive the study drug, divalproex sodium.

Drug: Divalproex sodium

Interventions

Divalproex sodium DRUG

Study drug.

Divalproex Sodium

Placebo DRUG

Placebo comparator.

Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Subjects with overall adaptive behavior scores below the age of two years on the Vineland Adaptive Behavior Rating Scale.
• Subjects with active or unstable epilepsy.
• Subjects with any of the following past or present mental disorders: schizophrenia, schizoaffective disorder or organic mental disorders.
• Subjects who are a serious suicidal risk.
• Subjects with clinically significant or unstable medical illness that would contraindicate participation in the study, including hematopoietic or cardiovascular disease, pancreatitis, liver toxicity, and polycystic ovary syndrome.
• Subjects reporting history of encephalitis, phenylketonuria, tuberous sclerosis, fragile X syndrome, anoxia during birth, pica, neurofibromatosis, hypomelanosis of Ito, hypothyroidism, Duchenne muscular dystrophy, and maternal rubella.
• Patients with history of the following:
• gastrointestinal, liver, or kidney, or other known conditions which will presently interfere presently with the absorption, distribution, metabolism, or excretion of drugs; cerebrovascular disease or brain trauma; clinically significant unstable endocrine disorder, such as hypo- or hyperthyroidism; recent history or presence of any form of malignancy
• Treatment within the previous 30 days with any drug known to a well-defined potential for toxicity to a major organ
• Subjects with clinically significant abnormalities in laboratory tests or physical exam.
• Subjects likely to require ECT or any other psychotropic medication during the study, unless otherwise permitted.
• Subjects unable to tolerate taper from psychoactive medication if necessary.
• Subjects with a history of hypersensitivity or severe side effects associated with the use of divalproex sodium, or other an ineffective prior therapeutic trial of divalproex sodium (serum levels within range of 50-100 ug/ml for 6 weeks).
• Subjects who have received any of the following interventions within the prescribed period before starting treatment:
• investigational drugs within the previous 30 days; depot neuroleptic medication; psychotropic drugs not permitted for concurrent use in the study within the previous seven days; fluoxetine within the previous five weeks.

Sponsors & Collaborators

• Montefiore Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (1)

• Iffland 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.

  PMID: 37811711 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Aggression

Interventions

Valproic Acid

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Eric Hollander
• Organization: Montefiore Medical Center

eholland@montefiore.org

718-920-4287

Study Officials

• Eric Hollander

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 21, 2005
• Study Start: September 1, 2002
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2008
• Last Updated: October 28, 2024
• Results First Posted: December 6, 2018

Record last verified: 2024-10

Locations

US (1)