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

NCT04007562 | Withdrawn

• 1 other identifier: APHP190368
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

LIPIN1 Deficiency

Keywords

LIPIN1 deficiency; Acute episodes of rhabdomyolysis; Myoglobinuria; Hydroxychloroquine Sulfate; Orphan drug

Outcome Measures

Primary Outcomes (3)

• Creatine kinase dosage in plasma

  36 months

• Inflammatory cytokines in plasma

  Quantitative flow cytometry based mutliplex assays (flow cytometry-based systems (BD™ Cytometric Bead Array)).

  36 months

• Quantification of mitochondrial DNA in plasma

  Quantitative PCR to detect mitochondrial DNA, 12s gene.

  36 months

Secondary Outcomes (16)

• Occurrence of intercurrent event

  36 months

• Occurrence of rash

  36 months

• Gowers sign appearance

  36 months

• Occurrence of shortness of breath

  36 months

• Occurrence of muscular fatigability

  36 months

Study Arms (1)

Lipin-1 deficiency

Patients suffering from Lipin-1 deficiency havebenefited from an off-label use treatment by Hydroxychloroquine Sulfate as part of their care for at least 6 months.

Drug: Hydroxychloroquine Sulfate

Interventions

Hydroxychloroquine Sulfate DRUG

The dosage and the route of administration of Hydroxychloroquine Sulfate was the same than in Lupus disease: Oral administration: administered in soluble form in patients under the age of 6 years old and administered in tablets in patients other the age of 6 years old with Lipin-1 deficiency. The soluble form was prepared at the Necker Hospital Pharmacy. Dose: 6.5 mg/kg/day (max 400 mg/day). The plasma concentration of the drug during follow-up was made, in order to follow a possible overdose.

Lipin-1 deficiency

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The population to be studied consists of 8 paediatric patients with Lipin-1 deficiency followed-up by the metabolic diseases center of Necker hospital and having been treated by Hydroxychloroquine sulfate for at least 6 months.

You may qualify if:

• Age ≥ 3 months
• Minors with Lipin-1 deficiency which were diagnosed with familiar context analysis followed by genetic diagnosis (two causal mutations on the LPIN1 gene) and treated by Hydroxychloroquine Sulfate off label use on a compassionate basis in the Metabolic Diseases Center of Necker Hospital
• Patients treated by Hydroxychloroquine Sulfate for at least 6 months

You may not qualify if:

• \- Opposition of parental authority holders

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

Related Publications (1)

• Hamel Y, Mauvais FX, Madrange M, Renard P, Lebreton C, Nemazanyy I, Pelle O, Goudin N, Tang X, Rodero MP, Tuchmann-Durand C, Nusbaum P, Brindley DN, van Endert P, de Lonlay P. Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis. Cell Rep Med. 2021 Aug 17;2(8):100370. doi: 10.1016/j.xcrm.2021.100370. eCollection 2021 Aug 17.

  PMID: 34467247 DERIVED

MeSH Terms

Conditions

Myoglobinuria

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Rhabdomyolysis; Muscular Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pascale de Lonlay, Professor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Caroline Tuchmann-Durand, Pharm. D

  Assistance Publique - Hôpitaux de Paris

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: July 5, 2019
• Study Start: November 4, 2019
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: September 25, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)