Bladder Cancer
Conditions
Keywords
Muscle-Infiltrating Urothelial Carcinoma, Neoadjuvant Chemotherapy, Standard of Care, Heart-Rate Variability, Biofeedback Intervention, Inflammation, Quality of Life, Cognitive Functions, Salivary Cortisol Slopes, Circadian Rhythms, Sleep Quality
Brief summary
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.
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.
Interventions
OTHERHRV biofeedback
Daily deep paced breathing 3-times (minimum 7 minutes each) for 3 months
Sponsors
Comenius University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Objective: Inflammation | 36 months | 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). |
| Primary Objective: Heart Rate Variability (HRV) | 36 months | 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. |
| Primary Objective: Quality of Life (QoL) | 36 months | 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. |
| Primary Objective: Working memory | 36 months | 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. |
| Primary objective: Executive function | 36 months | 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. |
| Primary objective: Salivary Cortisol Slopes | 36 months | 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). |
| Primary objective: Sleep Quality | 36 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary objective: Serious Adverse Events | 36 months | 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. |
| Secondary objective: Disease-Free Survival (DFS) | 60 months | 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). |
| Secondary objective: Overall Survival (OS) | 60 months | 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). |
Countries
Slovakia
Contacts
Primary ContactLuba Hunáková
Outcome results
None listed