Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism
Condition: Autism
MeSH terms: Autistic Disorder
Intervention: Divalproex sodium; Placebo
Intervention description: Study drug.; Placebo comparator.
Intervention MeSH terms: Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 5 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: autism; aggression; irritability; divalproex sodium

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.
    

Eligibility 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.