Ignite Creation Date:
2025-12-24 @ 11:05 PM
Ignite Modification Date:
2026-02-22 @ 11:02 AM
Study NCT ID:
NCT04174469
Status:
COMPLETED
Last Update Posted:
2020-09-02
First Post:
2019-05-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Ivermectin Neurotoxicity and ABCB1 Gene Mutations
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020258', 'term': 'Neurotoxicity Syndromes'}, {'id': 'D064420', 'term': 'Drug-Related Side Effects and Adverse Reactions'}], 'ancestors': [{'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D011041', 'term': 'Poisoning'}, {'id': 'D064419', 'term': 'Chemically-Induced Disorders'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood sample and DNA sample'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'RETROSPECTIVE', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 3}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2017-10-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-05', 'completionDateStruct': {'date': '2019-04-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-09-01', 'studyFirstSubmitDate': '2019-05-16', 'studyFirstSubmitQcDate': '2019-11-20', 'lastUpdatePostDateStruct': {'date': '2020-09-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2019-11-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-04-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Patient DNA sequencing', 'timeFrame': '1 day', 'description': 'Biological diagnostic: genotyping of ABCB1 (NM\\_000927.4) by using next generation sequencing (Agilent SureSelectQXT®, Miseq® Illumina). Bio-informatic analysis on JSI medical system GmbH sequence pilot CE v4.3.1 software.\n\nIdentified mutations were subsequently checked using Sanger sequencing on 3130XL (Applied Biosystems®). Bio-informatic analysis on SeqScape v2.5 software.'}], 'secondaryOutcomes': [{'measure': 'ivermectin dosage', 'timeFrame': '1 day', 'description': 'Biological diagnostic: blood test of ivermectin dosage (normal level: 46,6 (± 21,9) ng/mL for a single dose of 12 mg after 4H; and according to pharmacokinetics informations of VIDAL referential).'}, {'measure': 'cerebral spinal fluid dosages', 'timeFrame': '1 day', 'description': 'Cerebrospinal fluid test'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ivermectin', 'neurotoxicity', 'ATP binding cassette subfamily B member 1', 'ABCB1/P-glycoprotein (P-gp)', 'multidrug transporter', 'drug adverse event', 'Ivermectin toxicity'], 'conditions': ['DNA Sequencing']}, 'descriptionModule': {'briefSummary': "The study report a unique case of severe intoxication in a child treated with oral ivermectin to prevent scabies infection. The ABCB1 gene sequencing found the child compound heterozygote for two nonsense mutations, one in each gene copy. The child had inherited from each parent one of the alleles. Each mutation generate a predicted truncated protein that likely lead to ABCB1 loss of function, and the undesirable effects observed.\n\nThe study report a unique case of severe intoxication in a child treated with oral ivermectin to prevent scabies infection. The ABCB1 gene sequencing found the child compound heterozygote for two nonsense mutations, one in each gene copy. The child had inherited from each parent one of the alleles. Each mutation generate a predicted truncated protein that likely lead to ABCB1 loss of function, and the undesirable effects observed.\n\nWhile in some animals, nonsense ABCB1 mutations can lead to neurotoxicity of several ABCB1-substrate drugs, in humans, ivermectin was considered to have an especially high margin of safety, and nonsense mutations have never been reported before, nor has the neurotoxicity of ivermectin apparently caused by these two mutations never been reported before.\n\nThis discovery is of critical importance for the child, since it dictates that clinicians would need to optimize any ABCB1 substrate-based therapy in the future. More generally, such information must be brought to the attention of clinicians' medics, and in particular infectious disease specialists, pediatricians, and general practitioners.\n\nIt points the importance of pharmacovigilance, and the benefit of pharmacogenomic genotyping in well-defined phenotype, still too rarely considered in clinical practice before the implementation of a drug treatment.\n\nThis work results from a multidisciplinary approach, combining several areas of expertise in clinical pediatrics, pharmacology, biology, and bioinformatics."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '45 Years', 'minimumAge': '10 Years', 'samplingMethod': 'PROBABILITY_SAMPLE', 'studyPopulation': 'Child followed in the pediatric ward of Toulouse University Hospital for the episode of neurotoxicity and his parents', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* episode of neurotoxicity\n\nExclusion Criteria:\n\n* NA'}, 'identificationModule': {'nctId': 'NCT04174469', 'briefTitle': 'Ivermectin Neurotoxicity and ABCB1 Gene Mutations', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Montpellier'}, 'officialTitle': 'First Description of a Severe Ivermectin Neurotoxicity in a Child Carrying ABCB1 Nonsense Mutations.', 'orgStudyIdInfo': {'id': 'RECHMPL19_0176'}}, 'contactsLocationsModule': {'locations': [{'zip': '34295', 'city': 'Montpellier', 'country': 'France', 'facility': 'Uh Montpellier', 'geoPoint': {'lat': 43.61093, 'lon': 3.87635}}], 'overallOfficials': [{'name': 'Séverine CUNAT, PharmD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital, Montpellier'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED', 'description': 'NC'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Montpellier', 'class': 'OTHER'}, 'collaborators': [{'name': 'University Hospital, Toulouse', 'class': 'OTHER'}, {'name': 'INRAE, Toulouse France', 'class': 'UNKNOWN'}, {'name': 'Université Paris-Saclay, Gif-sur-Yvette, France', 'class': 'UNKNOWN'}, {'name': 'University Hospital, Montpellier France', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR'}}}}