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Trial record 52 of 106 for:    IVERMECTIN

Ivermectin Neurotoxicity and ABCB1 Gene Mutations

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04174469
Recruitment Status : Completed
First Posted : November 22, 2019
Last Update Posted : November 26, 2019
Sponsor:
Collaborators:
Toulouse University Hospital
National Veterinary School of Toulouse (INTHERES, UMR 1436, INRA, ENVT)
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief Summary:

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
DNA Sequencing

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Study Type : Observational
Actual Enrollment : 3 participants
Observational Model: Case-Only
Time Perspective: Retrospective
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

Resource links provided by the National Library of Medicine

Drug Information available for: Ivermectin




Primary Outcome Measures :
  1. Identified mutations Biological [ Time Frame: 1 day ]
    Biological diagnostic : genotyping by using next generation sequencing genetic screening of ABCB1 by using next generation sequencing


Secondary Outcome Measures :
  1. 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
Blood sample and DNA sample


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Child followed in the pediatric ward of Toulouse University Hospital for the episode of neurotoxicity and his parents
Criteria

Inclusion Criteria:

  • episode of neurotoxicity

Exclusion Criteria:

  • NA

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04174469


Locations
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France
Uh Montpellier
Montpellier, France, 34295
Sponsors and Collaborators
University Hospital, Montpellier
Toulouse University Hospital
National Veterinary School of Toulouse (INTHERES, UMR 1436, INRA, ENVT)
Investigators
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Principal Investigator: Séverine CUNAT, PharmD, PhD University Hospital, Montpellier

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Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT04174469    
Other Study ID Numbers: RECHMPL19_0176
First Posted: November 22, 2019    Key Record Dates
Last Update Posted: November 26, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: NC

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Montpellier:
ivermectin
neurotoxicity
ATP binding cassette subfamily B member 1
ABCB1/P-glycoprotein (P-gp)
multidrug transporter
drug adverse event
Ivermectin toxicity
Additional relevant MeSH terms:
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Neurotoxicity Syndromes
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Ivermectin
Antiparasitic Agents
Anti-Infective Agents