Ignite Creation Date:
2024-05-06 @ 1:21 PM
Last Modification Date:
2024-10-26 @ 1:13 PM
Study NCT ID:
NCT04007562
Status:
WITHDRAWN
Last Update Posted:
2022-11-08
First Post:
2019-05-29
Brief Title:
Acute Rhabdomyolysis and Muscle Pain Associated With Mutations in the LPIN1 Gene - A Retrospective Study Describing the Safety and Efficacy of Hydroxychloroquine Sulfate Given on a Compassionate Basis to Patients Suffering From Lipin-1 Deficiency
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Acute Rhabdomyolysis and Muscle Pain Associated With Mutations in the LPIN1 Gene - A Retrospective Study Describing the Safety and Efficacy of Hydroxychloroquine Sulfate Given on a Compassionate Basis to Patients Suffering From Lipin-1 Deficiency
Status:
WITHDRAWN
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
The study never started
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
LIPIN-1-METAB
Brief Summary:
Lipin-1 deficiencies are responsible for severe rhabdomyolysis and muscle pain in childhood A specific treatment does not exist Our research team Pr de Lonlay Pr Van-Endert Marine Madrange and Perrine Renard identified the mechanism of this disease and propose a treatment to decrease rhabdomyolysis outcome and muscle pain Further to a CPP approval in 2015 several patients have been treated by Hydroxychloroquine Sulfate off label use on a compassionate basis
The objective of this retrospective study is to describe the safety and efficacy of Hydroxychloroquine Sulfate given on a compassionate basis to patients suffering from Lipin-1 deficiency within a period between 6 and 36 months
The objective of this retrospective study is to describe the safety and efficacy of Hydroxychloroquine Sulfate given on a compassionate basis to patients suffering from Lipin-1 deficiency within a period between 6 and 36 months
Detailed Description:
The Lipin-1 deficiency is an inherited autosomal recessive disease caused by two mutations in the LPIN1 gene Homozygous or compound heterozygous Lipin-1 deficiency causes recurrent acute episodes of rhabdomyolysis and myoglobinuria in children associated with permanent muscle pain and weakness The onset of the disease is usually early before the age of 6 years old and the disease is severe The number of acute episodes ranges from 1 to 10 per patient mostly during the first 6 years of life period where illness episodes are most frequent Some patients die of myoglobinuric bouts from cardiac arrhythmia possibly due to hyperkalemia with a heart probably more sensitive to hyperkaliemia Mortality rate is around 10 and is significantly higher when rhabdomyolysis is complicated by renal failure or by cardiac arrest with arrhythmia due to hyperkalemia A specific treatment does not exist Altogether these observations indicate that there is a crucial need to identify a treatment
Our research team Pr de Lonlay Pr Van-Endert Marine Madrange and Perrine Renard identified the mechanism of this disease The consequences on myoblasts of patients are TLR9 sequestration in late endosomes and mitophagy impairment with consecutively mitochondrial DNA accumulation TLR9 activation inflammatory cytokines calcium release and cell death in the presence of TLR9 ligands and a nutrient-poor environment
Hydroxychloroquine Sulfate thanks to an anti-TLR9 activity restores control cell phenotypes In vivo and in vitro results are spectacular This treatment seems to be able to both decrease the signaling cascade resulting from the activation of TLR9 and to correct the phenotype of patients suffering from the Lipin-1 deficiency
Further to a CPP approval several patients have been treated by Hydroxychloroquine Sulfate off label use on a compassionate basis The objective of this retrospective study is to describe the safety and efficacy of Hydroxychloroquine Sulfate given on a compassionate basis to patients suffering from Lipin-1 deficiency within a period between 6 and 36 months
Our research team Pr de Lonlay Pr Van-Endert Marine Madrange and Perrine Renard identified the mechanism of this disease The consequences on myoblasts of patients are TLR9 sequestration in late endosomes and mitophagy impairment with consecutively mitochondrial DNA accumulation TLR9 activation inflammatory cytokines calcium release and cell death in the presence of TLR9 ligands and a nutrient-poor environment
Hydroxychloroquine Sulfate thanks to an anti-TLR9 activity restores control cell phenotypes In vivo and in vitro results are spectacular This treatment seems to be able to both decrease the signaling cascade resulting from the activation of TLR9 and to correct the phenotype of patients suffering from the Lipin-1 deficiency
Further to a CPP approval several patients have been treated by Hydroxychloroquine Sulfate off label use on a compassionate basis The objective of this retrospective study is to describe the safety and efficacy of Hydroxychloroquine Sulfate given on a compassionate basis to patients suffering from Lipin-1 deficiency within a period between 6 and 36 months
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None