Trial record 7 of 7 for:    Progeria

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT02056912
First received: January 24, 2014
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Lipodystrophy
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Identification of a New Gene Involved in Hereditary Lipodystrophy - LIPOGENE

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Additional mutation in the studied candidate gene XX [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Study's primary outcome

  • Altered lipids composition in blood red cells membranes [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Sub-study's primary outcome

  • Quantitative or qualitative variation of the protein encoded by the candidate gene in fibroblasts [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Sub-study's primary outcome

  • Dense deposits in fibroblasts cytoplasm [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Sub-study's primary outcome

  • Phospholipids anomalies in plasma [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Sub-study's primary outcome


Estimated Enrollment: 27
Study Start Date: January 2014
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Lipodystrophie Héréditaire 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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02056912

Contacts
Contact: Marie-Laure VUILLAUME 05 57 82 36 58 marie-laure.vuillaume@chu-bordeaux.fr
Contact: Cyril GOIZET 05 56 79 59 52 cyril.goizet@chu-bordeaux.fr

Locations
France
Service de Génétique Médicale Recruiting
Bordeaux, France, 33076
Contact: Marie-Laure VUILLAUME    05 57 82 36 58    marie-laure.vuillaume@chu-bordeaux.fr   
Contact: Cyril GOIZET    05 56 79 59 52    cyril.goizet@chu-bordeaux.fr   
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Marie-Laure VUILLAUME University Hospital, Bordeaux
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT02056912     History of Changes
Other Study ID Numbers: CHUBX 2013/13
Study First Received: January 24, 2014
Last Updated: February 5, 2014
Health Authority: France: Ministry of Health
France: ANSM

Keywords provided by University Hospital, Bordeaux:
lipodystrophy
gene
inborn error of metabolism

Additional relevant MeSH terms:
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on August 21, 2014