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NCT Number: NCT06194669

Mechanisms of Somatic Mutation and Tumor Initiation in Pre-malignant Kidney Tubule Cells

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.

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Key information

Conditions

Carcinoma, Renal Cell Abnormalities, Multiple Adenocarcinoma Angiomatosis Carcinoma Cardiovascular Diseases Ciliopathies Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Kidney Diseases Kidney Neoplasms Male Urogenital Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Neurocutaneous Syndromes Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Vascular Diseases Von Hippel-Lindau Disease

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Blood and urine sample collection

Other

One whole blood sample per individual (3 ml) will be collected. Up to 5 urine samples per individual will be collected

Primary outcomes

  1. Rate of somatic mutation accumulation in normal kidney tubule genomes

    Time frame: 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)

    The genome of multiple normal kidney cells from each subject will be investigated by whole genome sequencing. The number of somatic mutations per genome will be plotted according to donor's age and a curve describing the accumulation of mutations with age will be obtained for both the control and VHL-disease patient populations. The aim is to assess differences in mutation rates in the kidney of VHL-disease patients vs controls and understand the underlying mechanism.

Secondary outcomes

  1. Quantification of pre-cancer cells in urines

    Time frame: 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)

    From each urine sample, researchers can culture up to 20 single cell clones and perform a single-clone, gene-expression analysis. The expression of markers that characterize the mutation-prone, pre-cancer population will be assessed in all clones. The fraction of clones expressing markers of pre-cancer cells will be calculated in control and VHL-disease groups. The aim is to assess any differences in the presence of pre-cancer cells in urines from VHL-disease patients vs controls and assess any correlation of this parameter with kidney cancer occurrence.

Study contacts

Contact information is provided by the study sponsor or research team.

Daniela Canibus, BsC

CONTACT

[email protected]

+39 02 2643 5628

Irene Franco, PhD

CONTACT

[email protected]

+39 02 2643 2357

Sponsors and collaborators

Lead sponsor

IRCCS San Raffaele

Other

Collaborators

  • Università Vita-Salute San Raffaele

Registry information

Acronym: SoMuKT

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jan 8, 2024
Registry last updated
Jan 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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