Clinical trial NCT06194669: Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells
Official title: Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Carcinoma, Renal Cell
Von Hippel-Lindau Disease
Keywords: Somatic mutations
Whole genome sequencing
Normal kidney
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Università Vita-Salute San Raffaele
First posted: 2024-01-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with genetic diagnosis of VHL-disease, between 25 and 65, both genders

Brief summary: The goal of this observational study is to analyze somatic mutations in the genome of normal kidney cells from patients affected by kidney cancer predisposition syndrome Von Hippel Lindau (VHL) and compare the mutation rates observed in these patients and in individuals not affected by the disease. The main questions the study aims to answer are:

* Do kidney cells from VHL patients mutate more than cells from control individuals during adult life?
* What mechanisms favor somatic mutation occurrence in the genome of normal kidney tubule cells?

Participants will donate one blood sample and multiple urine samples. Urines will be used for kidney cell isolation, followed by cell culturing and genetic analyses. Urine samples will be collected once a year for 3-5 years. Sample collection will occur during the yearly screening program that each patient undergoes at the hospital. In case patients undergo surgical treatment of kidney tumors, samples discarded from surgery (tumor and normal kidney adjacent to tumor) will be collected and subjected to genetic analyses.

Researchers will compare the number and types of mutations found in tumors and normal kidney cells from VHL-disease patients with those found in normal kidney cells from control individuals, to see if somatic mutation rates are increased in VHL-disease patients during aging.


Eligibility criteria: Inclusion Criteria:

* Genetic diagnosis of VHL-disease; age (data need to be collected from a population distributed between 25 and 65 years); gender (males and females should be equally represented);

Exclusion Criteria:

* patients with bilateral nephrectomy, in dialysis or kidney transplant; use of nephrotoxic drugs

Primary outcomes:
measure: Rate of somatic mutation accumulation in normal kidney tubule genomes
timeFrame: Normal kidney tubule cells from urines are assessed from control and VHL-disease patients typically over a period of 3 years (min 3 months, max 3 years)
Secondary outcomes:
measure: Quantification of pre-cancer cells in urines
timeFrame: Normal kidney tubule cells from urines are assessed from control and VHL-disease patients typically over a period of 3 years (min 3 months, max 3 years)
Other outcomes:
Locations:
city: MIlan
country: Italy
facility: IRCCS Ospedale San Raffaele
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Irene Franco, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Ospedale San Raffaele
name: Alessandro Larcher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Ospedale San Raffaele
name: Andrea Salonia, MD
role: STUDY_CHAIR
References: