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Completed

NCT Number: NCT02954783

PROstaTe Cancer - Exercise-STudy (PRO-TEST)

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.

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Key information

Conditions

Prostate Cancer Behavior Genital Diseases Genital Diseases, Male Genital Neoplasms, Male Male Urogenital Diseases Motor Activity Neoplasms Neoplasms by Site Prostatic Diseases Prostatic Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Not applicable

Primary location

Center for Physical Activity Research, Copenhagen University Hospital

Copenhagen, DK-2100, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

High Intensity Interval Training

Behavioral

Supervised aerobic High Intensity Interval Training program consisting of 4 weekly sessions of approximately 35 minutes. Patients will perform a test of maximum cardio-respiratory (VO2 peak test). Using the patient's individual wattmax, a personalized exercise program will be prescribed.

After a light warm-up, patients will perform 25 min of aerobic high intensity interval training on a stationary bicycle, intervals will consist of cycles of HI intervals with 120% of wattmax for 1 min followed by recovery for 3 min at 30% of wattmax. Each session will be supervised by trained instructors to ensure proper technique, and progression in training load.

Usual Care Observational Control

Behavioral

The reference group will receive the standard patient care program as provided by the Department of Urology, Rigshospitalet.This includes information regarding smoking cessation and alcohol reduction and a physiotherapist consultation regarding pelvic floor exercises. This group is allowed to exercise on their own initiative or participate in any standard care hospital- or municipality-based exercise program. This will be monitored by self-report.

Primary outcomes

  1. Variability in intratumoral Natural Killer (NK)-cell infiltration

    Time frame: Primary prostate biopsies and up to 8 weeks

    Natural killer (NK)-cell infiltration will be quantified using histological analyses.

Secondary outcomes

  1. Tumor vessel morphology

    Time frame: Primary prostate biopsies and up to 8 weeks

    Tumor vessel morphology will be evaluated using histological analyses.

  2. Tumor-metabolism, - biology and signaling

    Time frame: Primary prostate biopsies and up to 8 weeks

    Tumor samples will undergo proteomic analyzes in order to uncover potential upregulated biomarkers.

  3. Changes in immune cells

    Time frame: Baseline and up to 8 weeks

    Quantification of immune cells will be measured in blood samples by flowcytometry analyses.

  4. Changes in epinephrine concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of epinephrine will be measured in blood samples by radioimmunoassay analyses.

  5. Changes in nor-epinephrine concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of nor-epinephrine will be measured in blood samples by radioimmunoassay analyses.

  6. Changes in IL-1 concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL-1 (Interleukin 1) will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  7. Changes in IL- 2 concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL-2 (Interleukin 2) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  8. Changes in IL- 6 concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL-6 (Interleukin 6) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  9. Changes in IL- 8 concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL-8 (Interleukin 8) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  10. Changes in IL- 10 concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL-10 (Interleukin 10) will be measured in fasting blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  11. Changes in IL- 15R alpha complex concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IL- 15Rα (IL- 15 receptor alpha) complex will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  12. Changes in Tumor Necrosis Factor alpha (TNFa) concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of TNFa will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  13. Changes in Interferon Gamma (IFNγ) concentration

    Time frame: Baseline and up to 8 weeks

    Concentrations of IFNγ will be measured in blood samples by Enzyme-Linked Immunosorbent Assay (ELISA) analyses.

  14. Changes in Plasma Total-Cholesterol concentrations

    Time frame: Baseline and up to 8 weeks

    Concentrations of total cholesterol will be measured in fasting blood samples by standard laboratory methods.

  15. Changes in Plasma LDL-Cholesterol concentrations

    Time frame: Baseline and up to 8 weeks

    Concentrations of LDL-cholesterol will be measured in fasting blood samples by standard laboratory methods

  16. Changes in Plasma HDL-Cholesterol concentrations

    Time frame: Baseline and up to 8 weeks

    Concentrations of HDL-cholesterol will be measured in fasting blood samples by standard laboratory methods

  17. Changes in Plasma Triglyceride concentrations

    Time frame: Baseline to and up to 8 weeks

    Concentrations of triglycerides will be measured in fasting blood samples by standard laboratory methods

  18. Changes in HbA1C (fasting blood samples)

    Time frame: Baseline and up to 8 weeks

    Concentrations of HbA1C will be measured in fasting blood samples by standard laboratory methods

  19. Changes in insulin

    Time frame: Baseline and up to 8 weeks

    Concentrations of Insulin will be measured in fasting blood samples by standard laboratory methods

  20. Change in body composition

    Time frame: Baseline and up to 8 weeks

    Body weight and anthropometrics (height, waist and hip circumference) will be assessed using standard procedures. Resting heart rate and blood pressure (Microlife, BPA100) will be determined in a supine position. Body composition (fat mass, bone mass and fat-free mass) and bone mineral density are analyzed by whole-body dual-energy X-ray absorptiometry (DXA) scan (Lunar, Lunar Corporation Madison, Wisconsin, USA). Transverse scans at 1 cm intervals are made from head to toe measuring the absorption of x-ray beams at two different energy levels as these are sent through the body. Since the different chemical compounds in the body absorb the intensity of the X-rays differently, the scan allows for a valid determination of bone mass, fat mass and fat-free/bone-free mass

  21. Change in VO2peak

    Time frame: Baseline and up to 8 weeks

    The participants will undergo a maximal graded exercise test on a bicycle ergometer for evaluation of cardiovascular function and determination of the peak oxygen uptake (VO2peak). The test starts with a 5 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. Ventilation and expired gases will be measured during the test via an indirect calorimetric system, and heart rate will be assessed simultaneously.

  22. Change in wattmax

    Time frame: Baseline and up to 8 weeks

    The participants 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 5 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.

  23. Changes in patient-reported Quality of Life - FACT

    Time frame: Baseline and up to 8 weeks

    Patient reported quality of life is measured by Functional Assessment of Cancer Treatment (FACT)

  24. Changes in Sleep Quality

    Time frame: Baseline up to 8 weeks

    Patient reported sleep quality is measured by the Pittsburgh Sleep Quality Index (PSQI) questionaire.

  25. Changes in Anxiety and Depression

    Time frame: Baseline up to 8 weeks

    Patient reported Anxiety and Depression is measured by the Hospital Anxiety and Depression Scale (HADS).

  26. Changes in Physical Activity level

    Time frame: Baseline up to 8 weeks

    Patient reported physical activity is measured by the International Physical Activity Questionaire (IPAQ) - short form.

  27. T-cell infiltration

    Time frame: Primary prostate biopsies from baseline and up to 8 weeks

    T-cell infiltration will be quantified using histological analyses.

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Registry information

Official study 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

Acronym: PRO-TEST

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
Nov 3, 2016
Registry last updated
Dec 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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