Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT00211757
First received: September 13, 2005
Last updated: April 15, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Autism
Drug: Divalproex sodium
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism

Resource links provided by NLM:


Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:
  • Clinical Global Impression-Improvement [ Time Frame: Study End ] [ Designated as safety issue: No ]
  • Change in Aberrant Behavior Checklist Scores [ Time Frame: Baseline and Study End ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: September 2002
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects in this arm will receive a placebo comparative to the study drug divalporex sodium.
Drug: Placebo
Placebo comparator.
Experimental: Divalporex Sodium
Subjects will receive the study drug, divalproex sodium.
Drug: Divalproex sodium
Study drug.

Detailed Description:

This study compares divalproex sodium and placebo in the treatment of autistic disorder. Twenty six child or adolescent outpatients, with age ranges from 5-17, will be randomized into a 12-week double-blind, placebo-controlled parallel treatment study. During the 12 weeks, patients will be monitored by the treating psychiatrist and assessed by an independent evaluator (IE). The IE will perform study assessments while remaining blind to medication regimens (including possible tapering) as well as any side effects. Study assessments will be administered at designated time points

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Meets DSM-IV, ADI, and ADOS criteria for autistic disorder

Age 5-17.

Outpatients

Parent/legal guardian signing informed consent, and assent documented for patient with demonstrated capacity to provide it.

Sexually active females of childbearing potential must use an acceptable method of birth control (oral contraceptive medications [the administration of which must be supervised by a parent or guardian], IUD, depot medication or tubal ligation) and have a negative serum pregnancy test prior to entry into the study.

Subject scores at least "4" (moderately ill) on the Clinical Global Impression-Severity Scale for Autistic Disorder (CGI-AD).

Subject meets the following criteria at pre-study diagnostic assessment and baseline assessment: OAS-M 13 or ABC-Irritability Subscale 18 (raw scores).

Subjects with history of seizures, who have been seizure-free for 6 months on a stable dose of anticonvulsant medication other than divalproex sodium or related formulations (e.g., depakene). Non-medicated subjects with a history of seizures who have been seizure-free for 6 months. Subjects with abnormal EEG but no clinical seizures.

State exclusion criteria for enrollment in study:

Subjects who are pregnant or nursing mothers. Sexually active women of childbearing potential who are not using adequate birth control measures (detailed above in inclusion criteria).

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.

Subjects who have begun any new alternative non-medication treatments, such as diet, vitamins, and psychosocial therapy, within the previous three months.

Subjects with any organic or systemic disease or patients who require a therapeutic intervention, not otherwise specified, which would confound the evaluation of the safety of the study medication.

Subjects who reside in a remote geographical area who do not have regular access to transportation to the clinical facility.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00211757

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Sponsors and Collaborators
Montefiore Medical Center
Investigators
Principal Investigator: Eric Hollander Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Eric Hollander, Montefiore Medical Center, Albert Einstein College of Medicine
ClinicalTrials.gov Identifier: NCT00211757     History of Changes
Other Study ID Numbers: GCO# 01-0294, IR21 NS43979
Study First Received: September 13, 2005
Last Updated: April 15, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:
autism
aggression
irritability
divalproex sodium

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on September 18, 2014