Clinical trial NCT03675529: The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy.
Official title: The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy - a Randomized Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prostate Cancer
Keywords: prostate neoplasm
exercise
high intensity interval training
tumor hypoxia
immune cells
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2018-09-18
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Men with histologically verified localized prostate adenocarcinoma undergoing curative intended radical prostatectomy.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Tumor hypoxia
timeFrame: At prostatectomy
Secondary outcomes:
measure: Intratumoral immune cell infiltration
timeFrame: Primary prostate biopsies and until radical prostatectomy
measure: Tumor vessel morphology
timeFrame: Primary prostate biopsies and until radical prostatectomy
measure: Tumor metabolism-, biology and signaling
timeFrame: Primary prostate biopsies and until radical prostatectomy
measure: Changes in immune cells during an acute exercise bout
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Changes in epinephrine concentration
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Changes in nor-epinephrine concentration
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Changes in various interleukines
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Changes in Tumor Necrosis Factor alpha (TNFa) concentration
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Changes in Interferon Gamma (IFNγ) concentration
timeFrame: From start of exercise bout and until 60 minutes post exercise
measure: Concentration of C-reactive Protein (CRP)
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Total plasma cholesterol concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Plasma LDL-Cholesterol concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Plasma HDL-Cholesterol concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Plasma triglyceride concentrations
timeFrame: Blood sampling on the day of radical prostatectomy
measure: HbA1C concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Plasma Insulin concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Plasma Glucose concentration
timeFrame: Blood sampling on the day of radical prostatectomy
measure: Wattmax-test
timeFrame: At baseline assessment
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for Physical Activity Research, Copenhagen University Hospital
Study officials:
affiliation: PhD student
name: Sissal S Djurhuus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Djurhuus SS, Schauer T, Simonsen C, Toft BG, Jensen ARD, Erler JT, Roder MA, Hojman P, Brasso K, Christensen JF. Effects of acute exercise training on tumor outcomes in men with localized prostate cancer: A randomized controlled trial. Physiol Rep. 2022 Oct;10(19):e15408. doi: 10.14814/phy2.15408.
citation: Schauer T, Djurhuus SS, Simonsen C, Brasso K, Christensen JF. The effects of acute exercise and inflammation on immune function in early-stage prostate cancer. Brain Behav Immun Health. 2022 Sep 7;25:100508. doi: 10.1016/j.bbih.2022.100508. eCollection 2022 Nov.