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The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy. (SHOR-TEST)

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ClinicalTrials.gov Identifier: NCT03675529
Recruitment Status : Recruiting
First Posted : September 18, 2018
Last Update Posted : January 25, 2019
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 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.


Condition or disease Intervention/treatment Phase
Prostate Cancer Behavioral: High Intensity Interval Training bout Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Effect of Exercise on Tumor Hypoxia in Men With Localized Prostate Cancer Undergoing Radical Prostatectomy - a Randomized Controlled Pilot Study
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Behavioral: High Intensity Interval Training bout
Patients randomized to the HIIT bout will perform one single supervised High Intensity Interval Training bout consisting firstly of a wattmax test on a stationary bike, in order to set the training intensity. This is followed by 10 minutes at low intensity at approximately 30% of wattmax. Subsequently patients will perform 16 min with 4 cycles with High and Low intensity. HI intervals consisting of 1 min with 100% of wattmax followed by 3 min recovery with the intensity load of 30% of wattmax.

No Intervention: Controls (usual care)
Patients randomized to the control group will not be doing any exercise, but will after approximately 35 min from baseline blood sampling receive one dose of pimonidazole hydrochloride (500 mg per m2 bodysurface) in order to quantify tumor hypoxia by pathological analyses after removal of the prostate by radical prostatectomy the following day.



Primary Outcome Measures :
  1. Tumor hypoxia [ Time Frame: At prostatectomy ]
    Quantification of tumor hypoxia will be assessed using pimonidazole staining


Secondary Outcome Measures :
  1. Intratumoral immune cell infiltration [ Time Frame: Primary prostate biopsies and until radical prostatectomy ]
    Intratumoral immune cell infiltration will be quantified using histological analyses

  2. Tumor vessel morphology [ Time Frame: Primary prostate biopsies and until radical prostatectomy ]
    Tumor vessel morphology will be evaluated using histological analyses

  3. Tumor metabolism-, biology and signaling [ Time Frame: Primary prostate biopsies and until radical prostatectomy ]
    Tumor samples will undergo proteomic analyses in order to uncover potential upregulated biomarkers

  4. Changes in immune cells during an acute exercise bout [ Time Frame: 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

  5. Changes in epinephrine concentration [ Time Frame: From start of exercise bout and until 60 minutes post exercise ]
    Concentration of epinephrine will be measured in blood samples by radioimmunoassay analyses.

  6. Changes in nor-epinephrine concentration [ Time Frame: From start of exercise bout and until 60 minutes post exercise ]
    Concentration of nor-epinephrine will be measured in blood samples by radioimmunoassay analyses.

  7. Changes in various interleukines [ Time Frame: 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.

  8. Changes in Tumor Necrosis Factor alpha (TNFa) concentration [ Time Frame: 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.

  9. Changes in Interferon Gamma (IFNγ) concentration [ Time Frame: 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.

  10. Concentration of C-reactive Protein (CRP) [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentration of CRP will be measured in fasting blood sample by standard laboratory methods.

  11. Total plasma cholesterol concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of total cholesterol will be measured in fasting blood samples by standard laboratory methods.

  12. Plasma LDL-Cholesterol concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of LDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.

  13. Plasma HDL-Cholesterol concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of HDL- cholesterol will be measured in fasting blood samples by standard laboratory methods.

  14. Plasma triglyceride concentrations [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of triglycerides will be measured in fasting blood samples by standard laboratory methods.

  15. HbA1C concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of HbA1C will be measured in fasting blood samples by standard laboratory methods.

  16. Plasma Insulin concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of insulin will be measured in fasting blood samples by standard laboratory methods.

  17. Plasma Glucose concentration [ Time Frame: Blood sampling on the day of radical prostatectomy ]
    Concentrations of glucose will be measured in fasting blood samples by standard laboratory methods.

  18. Wattmax-test [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Men with prostate cancer
Accepts Healthy Volunteers:   No
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

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): NCT03675529


Contacts
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Contact: Sissal S Djurhuus, MD 25705700 sissaldjurhuus@gmail.com
Contact: Jesper F Christensen, postdoc +4535456550 jesper.frank.christensen@regionh.dk

Locations
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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
Investigators
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Principal Investigator: Sissal S Djurhuus, MD PhD student

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Responsible Party: Sissal Sigmundsdóttir Djurhuus, Principal investigator, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT03675529     History of Changes
Other Study ID Numbers: H-18020711
First Posted: September 18, 2018    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sissal Sigmundsdóttir Djurhuus, Rigshospitalet, Denmark:
prostate neoplasm
exercise
high intensity interval training
tumor hypoxia
immune cells

Additional relevant MeSH terms:
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Prostatic Neoplasms
Hypoxia
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms