Ivermectin Neurotoxicity and ABCB1 Gene Mutations
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|ClinicalTrials.gov Identifier: NCT04174469|
Recruitment Status : Completed
First Posted : November 22, 2019
Last Update Posted : November 26, 2019
Our study report a unique case of severe adverse effects 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. To investigate this unique finding, the investigators also sequenced the ABCB1 gene of the child's parents and found evidence that the child had inherited from each parent one allele that would result in a truncated protein.
While 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 no nonsense mutations have been reported previously, nor has ivermectin neurotoxicity apparently caused by this double null mutation ever previously been reported in humans.
This finding 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, the investigators think that such information must be urgently brought to the attention of clinicians' medics, and in particular infectious disease specialists, pediatricians, and general practitioners. This is important in the context of worldwide increasing use of ivermectin. Our finding also illustrates the benefit of pharmacogenomic genotyping, still too rarely considered in clinical practice before the implementation of a drug treatment.
This work results from a multidisciplinary approach, combining the expertise of a pediatrician clinician, a pharmacologist, a biologist, and a researcher in pharmacology.
|Condition or disease|
|Study Type :||Observational|
|Actual Enrollment :||3 participants|
|Official Title:||First Description of a Severe Ivermectin Neurotoxicity in a Child Carrying ABCB1 Nonsense Mutations.|
|Actual Study Start Date :||October 10, 2017|
|Actual Primary Completion Date :||April 1, 2019|
|Actual Study Completion Date :||April 30, 2019|
- Identified mutations Biological [ Time Frame: 1 day ]Biological diagnostic : genotyping by using next generation sequencing genetic screening of ABCB1 by using next generation sequencing
- Identified Biological diagnostic [ Time Frame: 1 day ]blood and cerebral spinal fluid tests : 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).
Biospecimen Retention: Samples With DNA
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04174469
|Montpellier, France, 34295|
|Principal Investigator:||Séverine CUNAT, PharmD, PhD||University Hospital, Montpellier|