Biological Collection of Kidney Cells (CRHiPS)

• ClinicalTrials.gov Identifier: NCT03364504
• Recruitment Status: Unknown
• First Posted: December 6, 2017
• Last Update Posted: December 6, 2017
• Sponsor: University Hospital, Angers
• Collaborators: Université de Nantes; Hungarian Academy of Sciences
• Information provided by (Responsible Party): University Hospital, Angers

Tracking Information

• First Submitted Date: July 11, 2017
• First Posted Date: December 6, 2017
• Last Update Posted Date: December 6, 2017
• Estimated Study Start Date: January 2018
• Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2017)

Urine collection [ Time Frame: 24 hours ]

Three urine samples in each PXE in-patient consequences of the functional deficiency of the ABCC6 transporter involved in the pathophysiology of PXE

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: December 5, 2017)

• Isolation and culture of renal cells [ Time Frame: 8 weeks ]
  According to the routine procedure of our lab
• Impact of ABCC6 mutations on renal cell functions [ Time Frame: 3 months ]
  Proteomic and metabolomic and RNAseq approaches
• High throughput screening of drugs to restore ABCC6 function in PXE patients renal cells [ Time Frame: 3 months ]
  Evaluation of PPi release and other relevant readouts

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Biological Collection of Kidney Cells
• Official Title: Biological Collection of Renal Cells for the Functional Study of the ABCC6 Transporter on iPS-derived Hepatocytes and Renal Cells
• Brief Summary: Our objective is to obtain human induced pluripotent stem cells from urine samples of PXE patients for further proteomic and metabolomic studies and treatment screening.

Detailed Description

Pseudoxanthoma elasticum (PXE) is a genetic multysystem disorder with cutaneous, ophtalmological and cardiovascular involvement.

PXE is associated with mutations of ABCC6 gene coding for the membrane transporter ABCC6 protein. This transporter is normally expressed in hepatocytes and epithelial cells of renal proximal convoluted tubules.

Thus, PXE could be regarded as a metabolic disease of hepatic and renal origin, with clinical and biological involvement/consequences for remote organs.

The substance transported by ABCC6 protein being still unknown, ethiological PXE treatment does not exist yet. However, ABCC6 deficiency is associated with low level of blood PPi (pyrophosphate), which is natural inhibitor of calcium-phosphate deposition.

The aim of the project is to obtain the renal cells derived from PXE patients for their further usage in proteomic and metabolomic studies, as well as for screening of treatment modalities aimed to correct ABCC6 functional deficiency.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Pseudoxanthoma Elasticum

Intervention

Other: urine collection

3 urine collections during 24 hours

Study Arms

Experimental: PXE patients

urine collection and culture of renal cells

Intervention: Other: urine collection

Publications *

• Si-Tayeb K, Idriss S, Champon B, Caillaud A, Pichelin M, Arnaud L, Lemarchand P, Le May C, Zibara K, Cariou B. Urine-sample-derived human induced pluripotent stem cells as a model to study PCSK9-mediated autosomal dominant hypercholesterolemia. Dis Model Mech. 2016 Jan;9(1):81-90. doi: 10.1242/dmm.022277. Epub 2015 Nov 19.
• Chassaing N, Martin L, Calvas P, Le Bert M, Hovnanian A. Pseudoxanthoma elasticum: a clinical, pathophysiological and genetic update including 11 novel ABCC6 mutations. J Med Genet. 2005 Dec;42(12):881-92. doi: 10.1136/jmg.2004.030171. Epub 2005 May 13.
• Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Varadi A, Plomp A, Bergen AA, Oude Elferink RP, Borst P, van de Wetering K. ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1985-9. doi: 10.1161/ATVBAHA.114.304017. Epub 2014 Jun 26.
• Jansen RS, Kucukosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IE, Bergen AA, Gorgels TG, Borst P, van de Wetering K. ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20206-11. doi: 10.1073/pnas.1319582110. Epub 2013 Nov 25.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: December 5, 2017): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient with PXE diagnosed on clinical and histological criteria, according to current guidelines
• Patient aged over 18
• Patient informed, having understood the purpose and means of the study and signed the consent of participation
• Patient affiliated to the French social welfare system

Exclusion Criteria:

• Pregnant or nursing PXE woman
• Patient under guardianship, deprived of liberty by court or administrative decision, hospitalized without consent or admitted to a health or social institution for purposes other than research

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03364504
• Other Study ID Numbers: 49RC17_0063
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University Hospital, Angers
• Original Responsible Party: Same as current
• Current Study Sponsor: University Hospital, Angers
• Original Study Sponsor: Same as current

Collaborators

• Université de Nantes
• Hungarian Academy of Sciences

• Investigators: Not Provided
• PRS Account: University Hospital, Angers
• Verification Date: June 2017