- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02056912
Identification of a New Gene Involved in Hereditary Lipodystrophy (LIPOGENE)
January 13, 2015 updated by: University Hospital, Bordeaux
Identification of a New Gene Involved in Hereditary Lipodystrophy - LIPOGENE
Human lipodystrophies (lipoD) represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial.3, 4 Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications.
Acquired lipoD can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part.
The most common forms of lipoD are iatrogenic.
In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations.
Genetic forms are very uncommon: recessive generalized congenital lipoD result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2).
Dominant partial familial lipoD result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma.
Importantly, LMNA mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging.
Molecular genetic bases of many rare forms of genetic lipoD remain to be elucidated.
Study Overview
Status
Completed
Conditions
Detailed Description
The investigators have recently evaluated two sisters (index patients) affected by a syndrome associating diffuse leukoencephalopathy and partial lipoD.
The investigators have analyzed numerous known genetic causes of leukodystrophies and lipoD but the investigators failed to identify a known cause for this syndrome which has never been previously reported.
The investigators then switched their effort to analyses of exome using next generation sequencing in both affected sisters and their unaffected relatives (one sister and two parents).
The investigators identified an excellent candidate gene with a homozygous missense mutation in both affected sisters.
The investigators now aim to prove the involvement of this candidate gene in lipoD's determinism by a search of additional mutations in the candidate gene in a series of patients affected with lipoD (collaboration with Pr Capeau's Team) (LIPOGENE study) and by functional analyses performed in the two index patients on blood and skin samples (LIPOGENE sub-study).
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bordeaux, France, 33076
- Service de Génétique Médicale
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Study :
- Patients affected by lipoD
- No identified genetic cause of lipoD
- Child or adult
- DNA already available in the French reference laboratory for the genetic diagnosis of lipoD (laboratoire de Biochimie du CHU Saint-Antoine, Paris) or in the INSERM UMRS 938 laboratory, Faculté de médecine Pierre et Marie Curie Site Saint-Antoine, Paris
- Subject affiliated to the french Sécurité Sociale
- Signed consent obtained for the molecular diagnosis of lipoD.
Sub-study:
- Signed consent obtained for this sub-study from both index patients
Exclusion Criteria:
Study:
- Identified genetic cause of lipoD
- No signed consent by the patient
- Subject not affiliated to the french Sécurité Sociale.
Sub-study:
- Absence of signed consent obtained for this sub-study from both index patients
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Lipodystrophie Héréditaire
|
Performed only in the two index patients enrolled in the sub-study
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Additional mutation in the studied candidate gene XX
Time Frame: 6 months
|
Study's primary outcome
|
6 months
|
Altered lipids composition in blood red cells membranes
Time Frame: 6 months
|
Sub-study's primary outcome
|
6 months
|
Quantitative or qualitative variation of the protein encoded by the candidate gene in fibroblasts
Time Frame: 6 months
|
Sub-study's primary outcome
|
6 months
|
Dense deposits in fibroblasts cytoplasm
Time Frame: 6 months
|
Sub-study's primary outcome
|
6 months
|
Phospholipids anomalies in plasma
Time Frame: 6 months
|
Sub-study's primary outcome
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Marie-Laure VUILLAUME, University Hospital, Bordeaux
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2014
Primary Completion (ACTUAL)
January 1, 2014
Study Completion (ACTUAL)
January 1, 2014
Study Registration Dates
First Submitted
January 24, 2014
First Submitted That Met QC Criteria
February 5, 2014
First Posted (ESTIMATE)
February 6, 2014
Study Record Updates
Last Update Posted (ESTIMATE)
January 14, 2015
Last Update Submitted That Met QC Criteria
January 13, 2015
Last Verified
January 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CHUBX 2013/13
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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