NCT04174469

Ivermectin Neurotoxicity and ABCB1 Gene Mutations

Completed Last updated 2 September 2020

What this trial tests

trial in DNA Sequencing in 3 participants. Completed in 30 April 2019.

Timeline

10 October 2017

Primary endpoint
1 April 2019

30 April 2019

Quick facts

Lead sponsor	University Hospital, Montpellier
Status	Completed
Study type	OBSERVATIONAL
Enrollment	3
Start date	10 October 2017
Primary completion	1 April 2019
Estimated completion	30 April 2019
Sites	1 location across France

Conditions studied

• DNA Sequencing — all drugs for DNA Sequencing →

Sponsor

University Hospital, Montpellier

Who can join

Adults 10 to 45, any sex, with DNA Sequencing. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.