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

NCT04993859 | Recruiting DMC

• 3 other identifiers: 20-0680.ccP30CA0469341K23DK125673-01
• Study Type: observational
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Survivors of Childhood Cancer; Bladder Dysfunction

Outcome Measures

Primary Outcomes (5)

• 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 1. Group 1 vs. 2 2. Sub-analysis 1. Group 1a vs. 2a 2. Group 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

Study Arms (4)

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); Diagnostic Test: Urinary proteomic screen; Other: Dysfunctional Voiding Symptom Score Survey (DVSS)

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); Diagnostic Test: Urinary proteomic screen; Other: Dysfunctional Voiding Symptom Score Survey (DVSS)

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); Diagnostic Test: Urinary proteomic screen; Other: Dysfunctional Voiding Symptom Score Survey (DVSS)

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); Diagnostic Test: Urinary proteomic screen; Other: Dysfunctional Voiding Symptom Score Survey (DVSS)

Interventions

Non-invasive Urodynamic Test (niUDS) DIAGNOSTIC_TEST

A noninvasive urodynamics is a simple test used to evaluate urinary flow.

Female Cancer Survivors with DVSS Score < 6; Female Cancer Survivors with DVSS Score ≥ 6; Male Cancer Survivors with DVSS Score < 9; Male Cancer Survivors with DVSS Score ≥ 9

Urinary proteomic screen DIAGNOSTIC_TEST

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.

Female Cancer Survivors with DVSS Score < 6; Female Cancer Survivors with DVSS Score ≥ 6; Male Cancer Survivors with DVSS Score < 9; Male Cancer Survivors with DVSS Score ≥ 9

Dysfunctional Voiding Symptom Score Survey (DVSS) OTHER

The Dysfunctional Voiding Symptom Score provides accurate and objective grading of voiding behaviors of children.

Female Cancer Survivors with DVSS Score < 6; Female Cancer Survivors with DVSS Score ≥ 6; Male Cancer Survivors with DVSS Score < 9; Male Cancer Survivors with DVSS Score ≥ 9

Eligibility Criteria

• Age: 5 Years - 13 Years
• Gender Eligibility Details: Study groups and sub-groups will be assigned by gender
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• Children aged 5-13 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Cancer Institute (NCI): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• Children's Hospital Colorado: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Study Officials

• Nicholas Cost, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gemma Beltran

CONTACT

(720) 777-4418; gemma.beltran@childrenscolorado.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 6, 2021
• Study Start: June 2, 2021
• Primary Completion (Estimated): July 9, 2026
• Study Completion (Estimated): July 9, 2026
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 1 year after publication, for a total of 5 years
• Access Criteria: Written proposal with IRB approval

Locations

US (1)