Stress-reducing Intervention in Urothelial Carcinoma

A Study on Therapeutic Potential of Stress-reducing Intervention in Patients With Urothelial Carcinoma

The aim of this interventional study is to test the heart-rate variability biofeedback intervention (HRV BI) in patients with muscle-infiltrating bladder carcinoma (MIBC) treated with chemotherapy based on cisplatin in neoadjuvant setting followed by local therapy (standard of care, SOC) compared to SOC alone.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Other: HRV biofeedback

Detailed Description

This is a prospective, interventional, clinical study with a target of 50 subjects and an anticipated total duration of 36 months.

The goal of this study is to test the HRV BI in patients with MIBC treated with total of 3 to 4 courses of chemotherapy Gemcitabine 1000 mg/m2 + Cisplatin 70 mg/m2 day 1 (GC, new course day 22) or Methotrexate 30 mg/m2 day 1, Doxorubicin 30 mg/m2 day 2, Vinblastine 3 mg/m2 day 2, Cisplatin 70 mg/m2 day 2 with Pegfilgrastim 6 mg s.c. day 4 (ddMVAC, new course day 15) in neoadjuvant setting followed by radical cystectomy or irradiation concomitantly with cisplatin 70 mg/m2 weekly (SOC) and compare to SOC.

Participants will undergo 4 sessions of HRV BI with the trainer where they will learn about the prognostic role of the vagal nerve in cancer and in reducing distress and pain, and how to perform deep paced breathing with the HRV monitoring. They will perform the training daily (3-times, minimum 7 minutes each) at home with the online control for 3 months.

Researchers will compare the effect of addition of 3-months training of HRV BI to SOC on inflammation, HRV, quality of life (QoL), cognitive functions, salivary cortisol slopes, sleep quality and treatment outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luba Hunáková; Phone Number: +421290119943; Email: luba.hunakova@fmed.uniba.sk

Study Locations

• Slovakia
  • Bratislava, Slovakia, 83310
    • Recruiting
    • National Cancer Institute
    • Contact: Katarina Rejlekova; Email: katarina.rejlekova@nou.sk
    • Principal Investigator: Patrik Palacka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Patients older than 18 years.
2. Evidence of muscle-infiltrating urothelial bladder carcinoma (including variants) by biopsy.
3. No prior chemotherapy.
4. No previous malignancy, except for basal-cell carcinoma of the skin within last 5 years.
5. Adequate renal functions: measured or calculated (by Cockcroft formula) creatinine clearance > 60 ml/min.
6. Absolute granulocytes count 1,500/mm3 or higher, platelets 100,000/mm3 or higher, bilirubin 1.5x the upper limit of normal value and lower.
7. Adequate liver functions.
8. Basic computer skills.
9. Signed informed consent.

Exclusion criteria:

1. Diabetes mellitus with symptomatic neuropathy.
2. Using antiarrhythmic drugs, opiates and/or antidepressants.
3. Implanted permanent pacemaker (PPM).
4. Human Immunodeficiency Virus (HIV) infection.
5. Not fitting inclusion criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Heart-rate variability (HRV) biofeedback intervention + standard of care; Deep paced breathing with the HRV monitoring performed three times a day for seven minutes during three months with standard of care.	Other: HRV biofeedback; Daily deep paced breathing 3-times (minimum 7 minutes each) for 3 months; Other Names: physiologic
No Intervention: Standard of care; Gemcitabine 1000 mg/m2 + Cisplatin 70 mg/m2 day 1 (new course day 22) or Methotrexate 30 mg/m2 day 1, Doxorubicin 30 mg/m2 day 2, Vinblastine 3 mg/m2 day 2, Cisplatin 70 mg/m2 day 2 with Pegfilgrastim 6 mg s.c. day 4 (new course day 15) up to 4 courses followed by radical cystectomy or irradiation with cisplatin 70 mg/m2 weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective: Inflammation	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on inflammation (IL-6, Tumor necrosis factor α, IL-10 in pg/ml).	36 months
Primary Objective: Heart Rate Variability (HRV)	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on HRV indexed by the root mean square of successive differences between heartbeats (RMSSD) in ms.	36 months
Primary Objective: Quality of Life (QoL)	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on EORTC-QLQ-C30 (version 3) score. The EORTC-QLQ-C30 has 30 items divided into five functional scales (physical, role, cognitive, emotional, and social), and three symptom scales (fatigue, pain, and nausea and vomiting). The score for each scale as well as the sum score for the whole instrument is standardized to values 0 to 100, with a higher score meaning a worse outcome.	36 months
Primary Objective: Working memory	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on working memory measured by digit span test score (the number of remembered digits in the longest passed sequence), for both forward and backward condition.	36 months
Primary objective: Executive function	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on executive function measured by Stroop task mean response time for color-word condition.	36 months
Primary objective: Salivary Cortisol Slopes	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on salivary cortisol slopes (difference between bedtime and awakening saliva cortisol concentration in ng/ml).	36 months
Primary objective: Sleep Quality	The effect of 3-month heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on sleep quality measured by both actigraphy and self-report data. The main variables are total time spent sleeping (in hours and minutes), and sleep efficiency (proportion of time spent sleeping vs. time spent in bed trying to sleep).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary objective: Serious Adverse Events	The effect of 3-months heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on serious adverse events (SAEs) of chemotherapy.	36 months
Secondary objective: Disease-Free Survival (DFS)	The effect of 3-months heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on disease-free survival (DFS).	60 months
Secondary objective: Overall Survival (OS)	The effect of 3-months heart rate variability (HRV) biofeedback training and conventional cancer treatment (standard of care, SOC) vs. SOC alone on overall survival (OS).	60 months

Collaborators and Investigators

• Sponsor: Comenius University
• Investigators: Principal Investigator: Patrik Palacka, Faculty of Medicine, Comenius University in Bratislava

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2024
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 15, 2029

Study Registration Dates

• First Submitted: January 17, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Quality of Life; Sleep Quality; Standard of Care; Circadian Rhythms; Neoadjuvant Chemotherapy; Cognitive Functions; Muscle-Infiltrating Urothelial Carcinoma; Heart-Rate Variability; Biofeedback Intervention; Salivary Cortisol Slopes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell
• Other Study ID Numbers: UC-SK004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymised data of HRV, cognitive functions, quality of life, inflammatory markers, salivary cortisol, sleep quality, physical activity and psychological questionnaires.
• IPD Sharing Time Frame: Data will became available together with the publication and will be available for 5 years.
• IPD Sharing Access Criteria: Open.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

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