LIPIN1 DeficiencyLIPIN-1-METABNCT04007562
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
An observational study of LIPIN1 Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- LIPIN1 Deficiency
- What is being tested?
- Hydroxychloroquine Sulfate
- Type of treatment
- Pill or oral medicine
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 4 Nov 2019to 4 Nov 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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
Who cannot join
- Opposition of parental authority holders
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- LIPIN1 Deficiency
- Being tested
- Hydroxychloroquine Sulfate
- Keywords
- LIPIN1 deficiency, Acute episodes of rhabdomyolysis, Myoglobinuria, Hydroxychloroquine Sulfate, Orphan drug
- Medical subject headings
- Myoglobinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine SulfateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Hydroxychloroquine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Creatine kinase dosage in plasma
Measured: 36 months
Inflammatory cytokines in plasma
Quantitative flow cytometry based mutliplex assays (flow cytometry-based systems (BD™ Cytometric Bead Array)).
Measured: 36 months
Quantification of mitochondrial DNA in plasma
Quantitative PCR to detect mitochondrial DNA, 12s gene.
Measured: 36 months
Secondary outcomes (16)
Occurrence of intercurrent event
Clinical examination.
Measured: 36 months
Occurrence of rash
Clinical examination.
Measured: 36 months
Gowers sign appearance
Clinical examination.
Measured: 36 months
Occurrence of shortness of breath
Clinical examination.
Measured: 36 months
Occurrence of muscular fatigability
Clinical examination.
Measured: 36 months
Treatment compliance
Patient interrogation.
Measured: 36 months
Occurrence of adverse effect
Patient interrogation.
Measured: 36 months
Dosing of Hydroxychloroquine Sulfate in plasma
Compliance.
Measured: 36 months
Occurence of retinopathy.
Fundus eye and electroretinogram.
Measured: 36 months
Quotation of the different muscles
Muscle testing by a physiotherapist.
Measured: 36 months
6-min walking test
Measured: 36 months
Test of the number of steps during a 3-min walk
Measured: 36 months
Assessment of pain: VAS
Visual analogue scale (VAS) : scale from 1 to 10; compare from one examination to another for a patient (which is his own control).
Measured: 36 months
Quality-of-life assessment: Pediatric Quality of Life InventoryTM (PedsQL) questionnaire
Pediatric Quality of Life InventoryTM (PedsQL) questionnaire adapted to age: child questionnaire and parent questionnaire. Questionnaire of 23 questions scored on 5 points, from 0 (never) to 4 (almost always). The scores are linearly transformed on a scale between 0 and 100, added together and divided by the number of items completed; high scores are associated with a better quality of life related to health.
Measured: 36 months
Echocardiography
Measurement of the wall of the ventricles, ejection fraction.
Measured: 36 months
Absence of cardiac arrhythmia
Electrocardiography
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start4 Nov 2019
- Primary completion4 Nov 2019
- Study completion4 Nov 2019
Why it stopped: The study never started
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LIPIN1 DeficiencyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Pascale de Lonlay, Professor, Principal investigator, Assistance Publique - Hôpitaux de ParisCaroline Tuchmann-Durand, Pharm. D, Study director, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04007562
- Sponsor's protocol ID
- APHP190368
- Acronym
- LIPIN-1-METAB
- Status last verified
- Oct 2024
- First submitted
- 29 May 2019
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34467247
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04007562
- Acronym / sponsor ID
- LIPIN-1-METAB / APHP190368
- Conditions
- LIPIN1 Deficiency
- Keywords
- LIPIN1 deficiency, Acute episodes of rhabdomyolysis, Myoglobinuria, Hydroxychloroquine Sulfate, Orphan drug
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: The study never started
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 4 Nov 2019 (actual)
- Study completion
- 4 Nov 2019 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lipin-1 deficiency | – | Drug: Hydroxychloroquine SulfatePatients 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. |
Who may qualify
- Ages
- 3 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (1 listed)
- Opposition of parental authority holders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine SulfateThe 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. | Drug | Lipin-1 deficiency |
Primary outcome
Creatine kinase dosage in plasma
Time frame: 36 months
Inflammatory cytokines in plasma
Time frame: 36 months
Quantitative flow cytometry based mutliplex assays (flow cytometry-based systems (BD™ Cytometric Bead Array)).
Quantification of mitochondrial DNA in plasma
Time frame: 36 months
Quantitative PCR to detect mitochondrial DNA, 12s gene.
16 secondary outcomes
Occurrence of intercurrent event
Time frame: 36 months
Occurrence of rash
Time frame: 36 months
Gowers sign appearance
Time frame: 36 months
Occurrence of shortness of breath
Time frame: 36 months
Occurrence of muscular fatigability
Time frame: 36 months
Treatment compliance
Time frame: 36 months
Occurrence of adverse effect
Time frame: 36 months
Dosing of Hydroxychloroquine Sulfate in plasma
Time frame: 36 months
Occurence of retinopathy.
Time frame: 36 months
Quotation of the different muscles
Time frame: 36 months
6-min walking test
Time frame: 36 months
Test of the number of steps during a 3-min walk
Time frame: 36 months
Assessment of pain: VAS
Time frame: 36 months
Quality-of-life assessment: Pediatric Quality of Life InventoryTM (PedsQL) questionnaire
Time frame: 36 months
Echocardiography
Time frame: 36 months
Absence of cardiac arrhythmia
Time frame: 36 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Derived from this study: PubMed 34467247Hamel 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pascale de Lonlay, Professor principal investigator
Assistance Publique - Hôpitaux de Paris
Caroline Tuchmann-Durand, Pharm. D study director
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of LIPIN1 Deficiency, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Creatine kinase dosage in plasma (time frame: 36 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04007562, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.