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Ivermectin Neurotoxicity and ABCB1 Gene Mutations

NCT04174469 · Status: COMPLETED · Type: OBSERVATIONAL · Enrollment: 3

Last updated 2020-09-02

No results posted yet for this study

Summary

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.

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.

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 nonsense mutations have never been reported before, nor has the neurotoxicity of ivermectin apparently caused by these two mutations never been reported before.

This 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.

It 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.

This work results from a multidisciplinary approach, combining several areas of expertise in clinical pediatrics, pharmacology, biology, and bioinformatics.

Conditions

  • DNA Sequencing

Sponsors & Collaborators

  • University Hospital, Toulouse

    collaborator OTHER

  • INRAE, Toulouse France

    collaborator UNKNOWN

  • Université Paris-Saclay, Gif-sur-Yvette, France

    collaborator UNKNOWN

  • University Hospital, Montpellier France

    collaborator UNKNOWN

  • University Hospital, Montpellier

    lead OTHER

Principal Investigators

  • Séverine CUNAT, PharmD, PhD · University Hospital, Montpellier

Eligibility

Min Age
10 Years
Max Age
45 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2017-10-10
Primary Completion
2019-04-01
Completion
2019-04-30

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04174469 on ClinicalTrials.gov