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Identification of a New Gene Involved in Hereditary Lipodystrophy (LIPOGENE)

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ClinicalTrials.gov Identifier: NCT02056912
Recruitment Status : Completed
First Posted : February 6, 2014
Last Update Posted : January 14, 2015
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Tracking Information
First Submitted Date  ICMJE January 24, 2014
First Posted Date  ICMJE February 6, 2014
Last Update Posted Date January 14, 2015
Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 5, 2014)
  • Additional mutation in the studied candidate gene XX [ Time Frame: 6 months ]
    Study's primary outcome
  • Altered lipids composition in blood red cells membranes [ Time Frame: 6 months ]
    Sub-study's primary outcome
  • Quantitative or qualitative variation of the protein encoded by the candidate gene in fibroblasts [ Time Frame: 6 months ]
    Sub-study's primary outcome
  • Dense deposits in fibroblasts cytoplasm [ Time Frame: 6 months ]
    Sub-study's primary outcome
  • Phospholipids anomalies in plasma [ Time Frame: 6 months ]
    Sub-study's primary outcome
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Identification of a New Gene Involved in Hereditary Lipodystrophy
Official Title  ICMJE Identification of a New Gene Involved in Hereditary Lipodystrophy - LIPOGENE
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Condition  ICMJE Lipodystrophy
Intervention  ICMJE
  • Genetic: Amplification by PCR and direct sequencing on the entire coding sequence and intron-exons boundaries of the candidate gene
  • Biological: Perform blood cells and fibroblasts biochemical and immuno-labeled investigations
    Performed only in the two index patients enrolled in the sub-study
Study Arms  ICMJE Lipodystrophie Héréditaire
Interventions:
  • Genetic: Amplification by PCR and direct sequencing on the entire coding sequence and intron-exons boundaries of the candidate gene
  • Biological: Perform blood cells and fibroblasts biochemical and immuno-labeled investigations
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2015)
2
Original Estimated Enrollment  ICMJE
 (submitted: February 5, 2014)
27
Actual Study Completion Date  ICMJE January 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02056912
Other Study ID Numbers  ICMJE CHUBX 2013/13
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Bordeaux
Study Sponsor  ICMJE University Hospital, Bordeaux
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marie-Laure VUILLAUME University Hospital, Bordeaux
PRS Account University Hospital, Bordeaux
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP