Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2025-12-28 @ 6:50 AM
Study NCT ID:
NCT00211757
Status:
COMPLETED
Last Update Posted:
2024-10-28
First Post:
2005-09-13
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001321', 'term': 'Autistic Disorder'}, {'id': 'D000374', 'term': 'Aggression'}], 'ancestors': [{'id': 'D000067877', 'term': 'Autism Spectrum Disorder'}, {'id': 'D002659', 'term': 'Child Development Disorders, Pervasive'}, {'id': 'D065886', 'term': 'Neurodevelopmental Disorders'}, {'id': 'D001523', 'term': 'Mental Disorders'}, {'id': 'D000096762', 'term': 'Aberrant Motor Behavior in Dementia'}, {'id': 'D001526', 'term': 'Behavioral Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}, {'id': 'D012919', 'term': 'Social Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D014635', 'term': 'Valproic Acid'}], 'ancestors': [{'id': 'D010421', 'term': 'Pentanoic Acids'}, {'id': 'D014631', 'term': 'Valerates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D005232', 'term': 'Fatty Acids, Volatile'}, {'id': 'D005227', 'term': 'Fatty Acids'}, {'id': 'D008055', 'term': 'Lipids'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'eholland@montefiore.org', 'phone': '718-920-4287', 'title': 'Dr. Eric Hollander', 'organization': 'Montefiore Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '6 weeks on treatment', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.\n\nPlacebo: Placebo comparator.', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 8, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Divalproex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.\n\nDivalproex sodium: Study drug.', 'otherNumAtRisk': 16, 'deathsNumAtRisk': 16, 'otherNumAffected': 7, 'seriousNumAtRisk': 16, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Insomnia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Weight gian', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'polyuria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'agitation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 2}], 'organSystem': 'Immune system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT'}, {'term': 'Hypersomnolence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 11, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 16, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '1'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Number of Participants Reporting Improvement on the Clinical Global Impression', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.\n\nPlacebo: Placebo comparator.'}, {'id': 'OG001', 'title': 'Divalproex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.\n\nDivalproex sodium: Study drug.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to end of study (week 15)', 'description': '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', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Change in Aberrant Behaviors as Measured by the Aberrant Behavior Checklist Scores', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '16', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalporex sodium.\n\nPlacebo: Placebo comparator.'}, {'id': 'OG001', 'title': 'Divalproex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.\n\ndivalproex sodium: Study drug.'}], 'classes': [{'title': 'baseline', 'categories': [{'measurements': [{'value': '22', 'spread': '7.81', 'groupId': 'OG000'}, {'value': '20.3', 'spread': '7.36', 'groupId': 'OG001'}]}]}, {'title': 'Week 15', 'categories': [{'measurements': [{'value': '14.5', 'spread': '6.67', 'groupId': 'OG000'}, {'value': '17.7', 'spread': '7.94', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and End of Study (week 15)', 'description': '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.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.\n\nPlacebo: Placebo comparator.'}, {'id': 'FG001', 'title': 'Divalproex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.\n\nDivalproex sodium: Study drug.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '11'}, {'groupId': 'FG001', 'numSubjects': '16'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '14'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Lack of Efficacy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.\n\nPlacebo: Placebo comparator.'}, {'id': 'BG001', 'title': 'Divalporex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.\n\nDivalproex sodium: Study drug.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '27', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '13', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Diagnosis', 'classes': [{'categories': [{'title': 'Autistic Disorder', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '23', 'groupId': 'BG002'}]}, {'title': "Asperger's Syndrome", 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': "Subjects were either diagnosed with Autistic Disorder or Asperger's syndrome", 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 27}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2002-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2008-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-10-16', 'studyFirstSubmitDate': '2005-09-13', 'resultsFirstSubmitDate': '2018-05-29', 'studyFirstSubmitQcDate': '2005-09-13', 'lastUpdatePostDateStruct': {'date': '2024-10-28', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-12-05', 'studyFirstPostDateStruct': {'date': '2005-09-21', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-12-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2008-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of Participants Reporting Improvement on the Clinical Global Impression', 'timeFrame': 'Baseline to end of study (week 15)', 'description': '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'}, {'measure': 'Change in Aberrant Behaviors as Measured by the Aberrant Behavior Checklist Scores', 'timeFrame': 'Baseline and End of Study (week 15)', 'description': '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.'}]}, 'conditionsModule': {'keywords': ['autism', 'aggression', 'irritability', 'divalproex sodium'], 'conditions': ['Autism']}, 'referencesModule': {'references': [{'pmid': '37811711', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '5 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Meets DSM-IV, ADI, and ADOS criteria for autistic disorder\n\nAge 5-17.\n\nOutpatients\n\nParent/legal guardian signing informed consent, and assent documented for patient with demonstrated capacity to provide it.\n\nSexually 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.\n\nSubject scores at least "4" (moderately ill) on the Clinical Global Impression-Severity Scale for Autistic Disorder (CGI-AD).\n\nSubject meets the following criteria at pre-study diagnostic assessment and baseline assessment: OAS-M 13 or ABC-Irritability Subscale 18 (raw scores).\n\nSubjects 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.\n\nState exclusion criteria for enrollment in study:\n\nSubjects 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).\n\nSubjects with overall adaptive behavior scores below the age of two years on the Vineland Adaptive Behavior Rating Scale.\n\nSubjects with active or unstable epilepsy.\n\nSubjects with any of the following past or present mental disorders: schizophrenia, schizoaffective disorder or organic mental disorders.\n\nSubjects who are a serious suicidal risk.\n\nSubjects 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.\n\nSubjects 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.\n\nPatients with history of the following:\n\ngastrointestinal, 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\n\nTreatment within the previous 30 days with any drug known to a well-defined potential for toxicity to a major organ\n\nSubjects with clinically significant abnormalities in laboratory tests or physical exam.\n\nSubjects likely to require ECT or any other psychotropic medication during the study, unless otherwise permitted.\n\nSubjects unable to tolerate taper from psychoactive medication if necessary.\n\nSubjects 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).\n\nSubjects who have received any of the following interventions within the prescribed period before starting treatment:\n\ninvestigational 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.\n\nSubjects who have begun any new alternative non-medication treatments, such as diet, vitamins, and psychosocial therapy, within the previous three months.\n\nSubjects 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.\n\nSubjects who reside in a remote geographical area who do not have regular access to transportation to the clinical facility.'}, 'identificationModule': {'nctId': 'NCT00211757', 'briefTitle': 'Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism', 'organization': {'class': 'OTHER', 'fullName': 'Montefiore Medical Center'}, 'officialTitle': 'Divalproex Sodium vs. Placebo in Childhood/Adolescent Autism', 'orgStudyIdInfo': {'id': '01-0294'}, 'secondaryIdInfos': [{'id': '1R21NS043979', 'link': 'https://reporter.nih.gov/quickSearch/1R21NS043979', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Subjects in this arm will receive a placebo comparative to the study drug divalproex sodium.', 'interventionNames': ['Drug: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Divalproex Sodium', 'description': 'Subjects will receive the study drug, divalproex sodium.', 'interventionNames': ['Drug: Divalproex sodium']}], 'interventions': [{'name': 'Divalproex sodium', 'type': 'DRUG', 'description': 'Study drug.', 'armGroupLabels': ['Divalproex Sodium']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo comparator.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10029', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Mount Sinai School of Medicine', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}], 'overallOfficials': [{'name': 'Eric Hollander', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Icahn School of Medicine at Mount Sinai'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Montefiore Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Institute of Neurological Disorders and Stroke (NINDS)', 'class': 'NIH'}], 'responsibleParty': {'type': 'SPONSOR'}}}}