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PROstaTe Cancer - Exercise-STudy (PRO-TEST) (PRO-TEST)

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ClinicalTrials.gov Identifier: NCT02954783
Recruitment Status : Recruiting
First Posted : November 3, 2016
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
Sissal Sigmundsdóttir Djurhuus, Rigshospitalet, Denmark

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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Behavioral: High Intensity Interval Training Behavioral: Usual Care Observational Control Not Applicable

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 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
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 Start Date : November 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High Intensity Interval Training
The HIIT-group will receive usual care plus a supervised aerobic High Intensity Interval Training program consisting of 4 weekly sessions of approximately 35 minutes.
Behavioral: High Intensity Interval Training

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.


Active Comparator: Usual Care Observational Control
Patients randomized to usual care control will receive the standard patient care program as provided by the Department of Urology, Rigshospitalet.
Behavioral: Usual Care Observational Control
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 Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02954783


Contacts
Contact: Sissal S. Djurhuus, MD +4525705700 sissaldjurhuus@regionh.dk
Contact: Jesper F. Christensen, PhD +4535456550 jesper.frank.christensen@regionh.dk

Locations
Denmark
Center for Physical Activity Research, Copenhagen University Hospital Recruiting
Copenhagen, Denmark, DK-2100
Contact: Sissal S. Djurhuus, MD    +4525705700    sissaldjurhuus@regionh.dk   
Sponsors and Collaborators
Rigshospitalet, Denmark

Responsible Party: Sissal Sigmundsdóttir Djurhuus, MD, PhD student, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02954783     History of Changes
Other Study ID Numbers: H-16034670
First Posted: November 3, 2016    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Sissal Sigmundsdóttir Djurhuus, Rigshospitalet, Denmark:
Prostate cancer
Localized
Exercise
Physical activity
Natural killer cells
Immune cells

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases