Clinical trial NCT02954783: PROstaTe Cancer - Exercise-STudy (PRO-TEST)
Official title: Effect of Different Exercise Regimens on Intratumoral Natural Killer (NK) Cell Variability 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 cancer
Localized
Exercise
Physical activity
Natural killer cells
Immune cells
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2016-11-03
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: Background and purpose: The purpose of this study is to investigate the effect of exercise on intratumoral natural killer (NK)-cell variability in patients with localized prostate cancer undergoing radical prostatectomy.

The primary hypothesis is that exercise induces epinephrine-mediated intratumoral natural killer (NK)-cell infiltration in patients with localized prostate cancer, and that the infiltration is greater in patients performing High Intensity Interval Training compared to usual care controls.

Currently there is a lack of randomized controlled trials examining different types of exercise in patients with localized prostate cancer. 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 High Intensity Interval Training (HIIT) exercise intervention or observational control receiving usual care from inclusion and until planned surgery (radical prostatectomy).

All patients will undergo assessments at inclusion (baseline) and at follow-up after the exercise intervention period (maximum 8 weeks) 3-5 days prior to surgery.

Assessments include: anthropometrics; blood pressure; resting hearth rate; cardiorespiratory fitness by cardiopulmonary exercise test (VO2 peak.); body composition by DXA scan; quality of life by self-report questionnaires; fasting blood sample measuring cholesterol, triglycerides, insulin, c-peptide, HbA1c, glucose, hormones and inflammatory markers.

Biological tissue from tumor (primary prostate biopsies) will 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 exercise on the variability of intratumoral Natural Killer (NK)-cell infiltration in tumor biopsies taken before and after an exercise intervention in patients randomized 2:1 to one of two study arms: I) High Intensity Interval Training (HIIT) (N=20) or II) usual care, prior to radical prostatectomy.

In addition to this the investigators wish to investigate the effect of HIIT exercise on the infiltration of other immune cells into the tumor, tumor vessel morphology, modulation of tumor-metabolism, -biology and signaling.

Finally the aim is to explore the effect of pre-operative HIIT exercise on physiological (e.g. cardiovascular fitness, body composition, metabolic profile and metabolic inflammatory markers) and psycho-social (e.g. fatigue, emotional well-being, anxiety) endpoints relative to usual care.

Eligibility criteria: Inclusion Criteria:

* Pathologically verified localized prostate cancer
* Eligible for curative radical prostatectomy

Exclusion Criteria:

* Any other known malignancy requiring active treatment
* Performance status \> 1
* Ongoing treatment with beta blockers
* Physical disabilities precluding physical testing and/or exercise
* Inability to read and understand Danish

Primary outcomes:
measure: Variability in intratumoral Natural Killer (NK)-cell infiltration
timeFrame: Primary prostate biopsies and up to 8 weeks
Secondary outcomes:
measure: Tumor vessel morphology
timeFrame: Primary prostate biopsies and up to 8 weeks
measure: Tumor-metabolism, - biology and signaling
timeFrame: Primary prostate biopsies and up to 8 weeks
measure: Changes in immune cells
timeFrame: Baseline and up to 8 weeks
measure: Changes in epinephrine concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in nor-epinephrine concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL-1 concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL- 2 concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL- 6 concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL- 8 concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL- 10 concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in IL- 15R alpha complex concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in Tumor Necrosis Factor alpha (TNFa) concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in Interferon Gamma (IFNγ) concentration
timeFrame: Baseline and up to 8 weeks
measure: Changes in Plasma Total-Cholesterol concentrations
timeFrame: Baseline and up to 8 weeks
measure: Changes in Plasma LDL-Cholesterol concentrations
timeFrame: Baseline and up to 8 weeks
measure: Changes in Plasma HDL-Cholesterol concentrations
timeFrame: Baseline and up to 8 weeks
measure: Changes in Plasma Triglyceride concentrations
timeFrame: Baseline to and up to 8 weeks
measure: Changes in HbA1C (fasting blood samples)
timeFrame: Baseline and up to 8 weeks
measure: Changes in insulin
timeFrame: Baseline and up to 8 weeks
measure: Change in body composition
timeFrame: Baseline and up to 8 weeks
measure: Change in VO2peak
timeFrame: Baseline and up to 8 weeks
measure: Change in wattmax
timeFrame: Baseline and up to 8 weeks
measure: Changes in patient-reported Quality of Life - FACT
timeFrame: Baseline and up to 8 weeks
measure: Changes in Sleep Quality
timeFrame: Baseline up to 8 weeks
measure: Changes in Anxiety and Depression
timeFrame: Baseline up to 8 weeks
measure: Changes in Physical Activity level
timeFrame: Baseline up to 8 weeks
measure: T-cell infiltration
timeFrame: Primary prostate biopsies from baseline and up to 8 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Center for Physical Activity Research, Copenhagen University Hospital
Study officials:
References: