Ivermectin Neurotoxicity and ABCB1 Gene Mutations

NCT ID: NCT04174469

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 3 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-10-10
• Study Completion Date: 2019-04-30

Brief 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

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• episode of neurotoxicity

Exclusion Criteria

• NA

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: collaborator

INRAE, Toulouse France

UNKNOWN

Sponsor Role: collaborator

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

UNKNOWN

Sponsor Role: collaborator

University Hospital, Montpellier France

UNKNOWN

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Séverine CUNAT, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Montpellier

Locations

Uh Montpellier

Montpellier, , France

Countries

France

Other Identifiers

RECHMPL19_0176

Identifier Type: -

Identifier Source: org_study_id