The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy.
- Conditions
- Prostate Cancer
- Interventions
- Behavioral: High Intensity Interval Training bout
- Registration Number
- NCT03675529
- Lead Sponsor
- Rigshospitalet, Denmark
- Brief Summary
Background and purpose: The purpose of this study is to investigate the effect of one acute exercise bout on tumor hypoxia in patients with localized prostate cancer undergoing radical prostatectomy.
The primary hypothesis is that exercise reduces tumor hypoxia and that the reduction is greater in patients performing one acute high intensity exercise bout compared to no training controls.
The investigators have not been able to identify any prior or current randomized trials investigating exercise and tumor hypoxia, and believe that such research is warranted and would be of great importance. Moreover there is a need for studies including biological measurements to allow a full assessment of the effect of exercise on diverse biomarkers and mechanistic pathways, which may influence cancer survival.
Subjects: Patients with histologically verified prostate adenocarcinoma scheduled for radical prostatectomy at Urologic Department, Rigshospitalet, Copenhagen, Denmark.
Methods: In this randomized controlled pilot study 30 patients with localized prostate cancer undergoing radical prostatectomy will be included and randomized 2:1 to either one single acute High Intensity Interval Training bout or usual care and no training the day prior to radical prostatectomy.
All patients will undergo assessment at inclusion (baseline) and the day prior to surgery.
Assessment includes: anthropometrics; blood pressure; resting hearth rate; hip and waist circumference, ECG, quality of life by self-report questionnaires; fasting blood sample measuring PSA (prostate specific antigen), cholesterol, triglycerides, insulin, c-peptide, HbA1c, glucose and inflammatory markers.
All patients will receive one dose of pimonidazole hydrochloride (500 mg per m2 body surface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate.
Biological tissue from tumor (primary prostate biopsies) will also be retrieved from the respective local pathological departments and from the perioperative prostate specimen and sent to protocol analyses.
- Detailed Description
The purpose of this study is to investigate the effect of one acute exercise bout on tumor hypoxia in patients with localized prostate cancer randomized to one single acute I) High Intensity Interval Training bout compared to (II) usual care and no training prior to radical prostatectomy.
In addition to this the aim is to investigate the effect of one exercise bout on tumor vessel morphology and to investigate the effect of one acute exercise bout on intratumoral immune cell infiltration and to investigate the modulation of tumor-metabolism, -biology and signaling in patients randomized to either one acute High Intensity Interval Training bout compared to usual care and no training, the day prior to surgery.
Moreover this study will explore the acute response in immune cells, hormones and cytokines in blood samples taken before, during and after a single exercise session, and will collect physiological (metabolic profile and metabolic inflammatory markers) and psycho-social (e.g. fatigue, emotional well-being, anxiety) information regarding patients randomized to either one acute High Intensity Interval Training bout compared to usual care and no training, the day prior to surgery.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 30
- Men with histologically verified localized prostate adenocarcinoma undergoing curative intended radical prostatectomy.
- Age: <18 years
- Any other known malignancy requiring active treatment
- Performance status > 1
- Allergy to pimonidazole
- Ongoing treatment with beta blockers
- Physical disabilities precluding physical testing and/or exercise
- Inability to read and understand Danish
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High Intensity Interval Training bout High Intensity Interval Training bout Patients randomized to this group will perform a wattmax test immediately followed by 4 intervals of high and low intensity based on percentage of wattmax. Immediately after the exercise bout is finished patients will receive one dose of pimonidazole hydrochloride (500 mg per m2 body surface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate by radical prostatectomy the following day.
- Primary Outcome Measures
Name Time Method Tumor hypoxia At prostatectomy Quantification of tumor hypoxia will be assessed using pimonidazole staining
- Secondary Outcome Measures
Name Time Method Changes in immune cells during an acute exercise bout From start of exercise bout and until 60 minutes post exercise Changes in immune cells during an acute exercise bout will be measured in blood samples using flowcytometry
Changes in epinephrine concentration From start of exercise bout and until 60 minutes post exercise Concentration of epinephrine will be measured in blood samples by radioimmunoassay analyses.
HbA1C concentration Blood sampling on the day of radical prostatectomy Concentrations of HbA1C will be measured in fasting blood samples by standard laboratory methods.
Wattmax-test At baseline assessment The participants in the HIIT group will undergo a maximal graded exercise test on a bicycle ergometer for evaluation of cardiovascular function and determination of the maximum watt (wattmax). The test starts with a 3 min warm up at 70 watt (the watts may have to be adjusted to the individual fitness level). Warm up is immediately followed by a 20 watt increase every 1 min until exhaustion. The maximum watt will be calculated.
Changes in various interleukines From start of exercise bout and until 60 minutes post exercise Concentration of various interleukines will be measured in blood samples by measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.
Changes in Interferon Gamma (IFNγ) concentration From start of exercise bout and until 60 minutes post exercise Concentrations of IFNγ will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.
Plasma HDL-Cholesterol concentration Blood sampling on the day of radical prostatectomy Concentrations of HDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.
Plasma triglyceride concentrations Blood sampling on the day of radical prostatectomy Concentrations of triglycerides will be measured in fasting blood samples by standard laboratory methods.
Plasma Insulin concentration Blood sampling on the day of radical prostatectomy Concentrations of insulin will be measured in fasting blood samples by standard laboratory methods.
Plasma Glucose concentration Blood sampling on the day of radical prostatectomy Concentrations of glucose will be measured in fasting blood samples by standard laboratory methods.
Intratumoral immune cell infiltration Primary prostate biopsies and until radical prostatectomy Intratumoral immune cell infiltration will be quantified using histological analyses
Changes in Tumor Necrosis Factor alpha (TNFa) concentration From start of exercise bout and until 60 minutes post exercise Concentrations of TNFa will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.
Tumor metabolism-, biology and signaling Primary prostate biopsies and until radical prostatectomy Tumor samples will undergo proteomic analyses in order to uncover potential upregulated biomarkers
Changes in nor-epinephrine concentration From start of exercise bout and until 60 minutes post exercise Concentration of nor-epinephrine will be measured in blood samples by radioimmunoassay analyses.
Concentration of C-reactive Protein (CRP) Blood sampling on the day of radical prostatectomy Concentration of CRP will be measured in fasting blood sample by standard laboratory methods.
Total plasma cholesterol concentration Blood sampling on the day of radical prostatectomy Concentrations of total cholesterol will be measured in fasting blood samples by standard laboratory methods.
Plasma LDL-Cholesterol concentration Blood sampling on the day of radical prostatectomy Concentrations of LDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.
Tumor vessel morphology Primary prostate biopsies and until radical prostatectomy Tumor vessel morphology will be evaluated using histological analyses
Trial Locations
- Locations (1)
Center for Physical Activity Research, Copenhagen University Hospital
🇩🇰Copenhagen, Denmark