CASUS: Improved and Quality Assured Collection of First-void Urine

Study Overview
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Brief Summary
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The goal of the overall CASUS project is to develop the first fully molecular integrated cervical cancer screening approach, based on first-void urine as an easily accessible and non-invasive source of biomarkers. In contrast to current screening modalities, the CASUS approach will identify women with clinically relevant disease in need of treatment using only a single sample that can be collected at home (one-step triage).

Detailed Description
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CASUS work package 1 (WP1): To accommodate for the detection of biomarkers in first-void urine, a next-generation first-void urine collection device is necessary, which includes internal process control, novel collector tubes for collection of smaller urine volumes, and integration of a non-toxic nucleic acid preservative. Hereto, new generations of the Colli-Pee® (Novosanis) first-void urine collector allowing collection of smaller volumes (Colli-Pee Small Volumes 4 and 10 mL) next to the 'standard' Colli-Pee FV5000 (20 mL) first-void urine collector will be developed and validated. The optimal urine volume needed for detection of host and viral biomarkers, as well as optimization of the nucleic acid preservative solution by introduction of a sample/extraction validation control (non-human DNA internal control (DNA IC)) will be evaluated by measuring the concentration of human DNA, HPV DNA, and the DNA IC in all first-void urine samples using different DNA extraction protocols.

Official Title
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Developing a Complete Cervical Cancer Screening Solution Based on First-void Urine Self-sampling: Improved and Quality Assured Collection of First-void Urine

Conditions
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Urine, Cervical Cancer, Cervical Intraepithelial Neoplasia, Human Papilloma Virus, HPV-Related Cervical Carcinoma

Intervention / Treatment
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* Device: Colli-Pee® (FV5000 and Small Volumes)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female 18 years and older Women with a high-risk HPV positive test result within six months prior to study enrolment. Giving informed consent to the research team to contact his/her general practitioner and/or gynaecologist to access details of the participants HPV test results and cervical screening history. Able to understand the information brochure/what the study is about. Exclusion Criteria: Women that underwent hysterectomy or were treated for cervical (pre)cancer lesions within the previous six months prior to study enrolment. Participating in another interventional clinical study (where e.g. a medical device, drug, or vaccine is evaluated) at the same time of participating in this study. Participation in another observational or low-interventional clinical study at the same time is allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: First-void urine collection<br>Women self-collect three first-void urine samples (random order) at home. | Device: Colli-Pee® (FV5000 and Small Volumes)<br>* Colli-Pee® device (Novosanis, Belgium) attached to collector tubes prefilled with a non-toxic nucleic acid preservative (including an internal process control). The collector tubes differ in size to collect a total sample volume of 4, 10, and 20 mL. Each participant will collect three urine samples using the Colli-Pee Small Volumes 4 and 10 mL, and the Colli-Pee FV5000 (20 mL) device, in a random order.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human DNA (GAPDH) | Comparison of human DNA (GAPDH) concentrations [cycle threshold values] between first-void urine volumes (4, 10, 20 mL) and extraction methods measured by quantitative PCR (qPCR). | Evaluation/testing when all samples are collected [1 year] | 
| Internal control DNA (IC DNA) | Comparison of internal control DNA (IC DNA) concentrations [cycle threshold values] between first-void urine volumes (4, 10, 20 mL) and extraction methods measured by quantitative PCR (qPCR). | Evaluation/testing when all samples are collected [1 year] | 
| Human DNA reference gene (ACTB) | Comparison of human DNA reference gene (ACTB) concentrations [cycle threshold values] between first-void urine volumes (4, 10, 20 mL) and extraction methods measured by quantitative methylation specific PCR (qMSP). | Evaluation/testing when all samples are collected [1 year] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human DNA (Beta-globin) | Comparison of human DNA (Beta-globin) concentrations [cycle threshold values] between first-void urine volumes (4, 10, 20 mL) and extraction methods measured using the HPV-risk assay (Self-Screen BV). | Evaluation/testing when all samples are collected [1 year] | 
| HPV DNA (HPV16, HPV18, other high-risk HPV (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68)) | Comparison of HPV DNA (HPV16, HPV18, other high-risk HPV (HPV31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68)) positivity (+/-) and concentrations [cycle threshold values] between first-void urine volumes (4, 10, 20 mL) and extraction methods measured using the HPV-risk assay (Self-Screen BV). | Evaluation/testing when all samples are collected [1 year] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Biomarker, First-void urine, Screening, Triage