Impact of Chemotherapy on Urinary Biomarkers and Non-Invasive Urodynamics in Children

The over-arching aim of this study is to evaluate the effects of two specific anti-cancer chemotherapies, vincristine and doxorubicin, on bladder function and urine composition.

Study Overview

• Status: Recruiting
• Conditions: Bladder Dysfunction; Survivors of Childhood Cancer
• Intervention / Treatment: Diagnostic test: Non-invasive Urodynamic Test (niUDS); Diagnostic test: Urinary proteomic screen; Other: Dysfunctional Voiding Symptom Score Survey (DVSS)

Detailed Description

The over-arching aim of this study is to evaluate the effects of two specific anti-cancer chemotherapies, vincristine and doxorubicin, on bladder function and urine composition. The global hypothesis is that childhood cancer survivors with prior exposure to systemic vincristine (VCR) and/or doxorubicin (DOX) report an increased incidence of bladder dysfunction (BD) symptoms on the Dysfunctional Voiding Symptom Score (DVSS) survey. We expect to observe differences in non-invasive urodynamic (niUDS) testing between childhood cancer survivors with BD symptoms on the DVSS versus those without BD symptoms on DVSS. We also expect to observe statistically significant differences in the urinary levels of known urinary biomarkers of BD (NGF, ATP and BDNF) of patients with evidence of BD compared to those without BD on the DVSS. We also expect to observe rational differences in the urinary proteome of patients between those with and without BD.

• Study Type: Observational
• Enrollment (Estimated): 152

Contacts and Locations

• Study Contact: Name: Gemma Beltran; Phone Number: (720) 777-4418; Email: gemma.beltran@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Gemma Beltran; Phone Number: 720-777-4418; Email: gemma.beltran@childrenscolorado.org
      • Principal Investigator: Nicholas Cost, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 10 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Childhood cancer survivors that have been treated with a chemotherapy regimen including VCR and/or DOX, completion of chemotherapy at least one year prior to study enrollment and survey completion.

Description

Inclusion Criteria:

• Children aged 5-10 years old
• A history of cancer
• Treatment with a chemotherapy regimen including VCR and/or DOX
• Completion of chemotherapy at least one year prior to study enrollment and survey completion.

Exclusion Criteria:

• Patients with a:
• Primary pelvic tumor
• Pelvic irradiation
• Pre-existing bladder/bowel dysfunction
• Spinal defects
• Neurologic disorder
• Neuro-oncologic tumor or brain metastasis
• Cyclophosphamide or ifosfamide therapy

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Male Cancer Survivors with DVSS Score ≥ 9; Childhood cancer survivors treated with DOX and/or VCR with evidence of BD on DVSS	Diagnostic test: Non-invasive Urodynamic Test (niUDS); A noninvasive urodynamics is a simple test used to evaluate urinary flow.; Diagnostic test: Urinary proteomic screen; Urine proteomics is a powerful platform to identify urinary excreted proteins and peptides in different stages of disease or therapy and to determine their quantity, functions, and interaction.; Other: Dysfunctional Voiding Symptom Score Survey (DVSS); The Dysfunctional Voiding Symptom Score provides accurate and objective grading of voiding behaviors of children.
Female Cancer Survivors with DVSS Score ≥ 6; Childhood cancer survivors treated with DOX and/or VCR with evidence of BD on DVSS	Diagnostic test: Non-invasive Urodynamic Test (niUDS); A noninvasive urodynamics is a simple test used to evaluate urinary flow.; Diagnostic test: Urinary proteomic screen; Urine proteomics is a powerful platform to identify urinary excreted proteins and peptides in different stages of disease or therapy and to determine their quantity, functions, and interaction.; Other: Dysfunctional Voiding Symptom Score Survey (DVSS); The Dysfunctional Voiding Symptom Score provides accurate and objective grading of voiding behaviors of children.
Male Cancer Survivors with DVSS Score < 9; Childhood cancer survivors treated with DOX and/or VCR without evidence of BD on DVSS	Diagnostic test: Non-invasive Urodynamic Test (niUDS); A noninvasive urodynamics is a simple test used to evaluate urinary flow.; Diagnostic test: Urinary proteomic screen; Urine proteomics is a powerful platform to identify urinary excreted proteins and peptides in different stages of disease or therapy and to determine their quantity, functions, and interaction.; Other: Dysfunctional Voiding Symptom Score Survey (DVSS); The Dysfunctional Voiding Symptom Score provides accurate and objective grading of voiding behaviors of children.
Female Cancer Survivors with DVSS Score < 6; Childhood cancer survivors treated with DOX and/or VCR without evidence of BD on DVSS	Diagnostic test: Non-invasive Urodynamic Test (niUDS); A noninvasive urodynamics is a simple test used to evaluate urinary flow.; Diagnostic test: Urinary proteomic screen; Urine proteomics is a powerful platform to identify urinary excreted proteins and peptides in different stages of disease or therapy and to determine their quantity, functions, and interaction.; Other: Dysfunctional Voiding Symptom Score Survey (DVSS); The Dysfunctional Voiding Symptom Score provides accurate and objective grading of voiding behaviors of children.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of non-normal niUDS patterns between groups	a. Patterns will be scored by blinded reviewers b. Will calculate an Inter-rater Kappa correlation co-efficient i. Utilize consensus review for discrepancies between reviewers and between the patient's 1st/2nd niUDS for the final assignment ii. Will calculate an intra-test reliability (compare correlation between 1st and 2nd patter) c. Chi-square test to compare proportions of non-normal vs. normal pattern type i. Group 1a vs. 2a ii. Group 1b vs. 2b d. Sample Size Calculation: Based on published data of niUDS patterns in children with normal bladder function, we expect 15% of those children in Group 2 to have non-normal niUDS patterns. We hypothesize that 40% of children in Group 1 to have non-normal niUDS patterns. 38 subjects in each gender sub-group provide 80% power to detect this 25% difference with an one-sided chi-square test with an alpha of 0.05.	Immediately after niUDS done at the first visit
Proportion of Elevated Post-Void Residual (PVR) between groups	a. Will use an "average PVR" between the 1st/2nd niUDS for the analysis b. Chi-square test to compare proportions of elevated PVR i. Group 1a vs. 2a ii. Group 1b vs. 2b c. Sample Size Calculation: Based on published data of PVR in children with normal bladder function, we expect 1.5% of those children in Group 2 to have elevated PVR. We hypothesize that 25% of children in Group 1 to have an elevated PVR. 21 subjects in each gender sub-group provide 80% power to detect this 23.5% difference with an one-sided chi-square test with an alpha of 0.05.	13 months
Compare Peak Flow Rates (Qmax) between groups	a. Will use the average of the two Qmax between the 1st/2nd flow rate for the analysis b. Two group t-test for comparing continuous variables (Qmax) i. Group 1a vs. 2a ii. Group 1b vs. 2b c. Sample Size Calculation: 38 subjects in Group 1a and 2a provide 80% power to detect an effect size of 0.7 (mean difference divided by the common standard deviation) using a 2-sided two-group test with an alpha of 0.05. if the outcome is not normally distributed, transformation will be carried out so the distribution will be approximately normal. This power calculation also applies to the comparison between Group 1b vs 2b	13 momths
Compare Average Flow Rates (Qavg) for age/gender	a. Will use the average of the two Qavg between the 1st/2nd flow rate for the analysis b. Two group ttest for comparing continuous variables (Qavg) i. Group 1a vs. 2a ii. Group 1b vs. 2b c. See the power calculation in 3c.	13 months
Compare Urinary Biomarker Levels between groups	1. Compare urinary biomarker levels between groups i. ATP, BDNF, NGF ii. Two-group t-test for comparing continuous variables; Group 1 vs. 2; Sub-analysisGroup 1a vs. 2aGroup 1b vs. 2b The sample size calculation in 1d can apply to each biomarker. Based on published data in other populations with BD, for NGF, ATP and BDNF, we hypothesize to detect a difference of these urinary biomarkers 2x higher in Group 2 (Elevated DVSS scores) vs. Group 1 (Normal DVSS scores). A mixed effects model will be used to estimate and compare a biomarker expression between the two groups by incorporating the individual measurements on each subject into the model, where gender and group assignment will be the predictor. Interaction term between group and gender will be considered to study the effect modification by gender on a biomarker if possible.	13 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Cancer Institute (NCI); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Children's Hospital Colorado
• Investigators: Principal Investigator: Nicholas Cost, MD, Children's Hospital Colorado

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2021
• Primary Completion (Estimated): July 9, 2024
• Study Completion (Estimated): July 9, 2025

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 21, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 20-0680.cc; P30CA046934 (U.S. NIH Grant/Contract); 1K23DK125673-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient Data will be shared after written request to study PI and after approval by local IRB and study committee
• IPD Sharing Time Frame: 1 year after publication, for a total of 5 years
• IPD Sharing Access Criteria: Written proposal with IRB approval
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No