PROState Cancer Patients Initiating Hormone Therapy: Effect of Exercise on CARDIOvascular Health (PROSCARDIO) (PROSCARDIO)
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Standard care plus exercise
Sponsored by
About this trial
This is an interventional prevention trial for Prostate Cancer focused on measuring Prostate Cancer, Androgen deprivation therapy, Exercise
Eligibility Criteria
Inclusion Criteria:
- Male
- Aged 50 to 80 years
- Histologically confirmed stage I-IV prostate cancer
- Scheduled for treatment with a luteinizing hormone-releasing hormone (LHRH) agonist either alone or combined with radiotherapy
- Anticipated to remain on androgen deprivation therapy (ADT) for at least the next 6 months
- Willing and able to give written informed consent.
- Understand written and verbal instructions in English
- World Health Organisation (WHO) performance status 0 to 1
Exclusion Criteria:
- Previously treated with ADT
- Diagnosed or suspected metastatic bone disease
- Absolute contraindications to exercise testing and training as defined by the American College of Sports Medicine (ACSM, 2010)
- Prior myocardial infarction or heart failure
- Chronic obstructive pulmonary disease (COPD)
- Poorly controlled hypertension (≥ 200/110 mmHg)
- Uncontrolled supraventricular tachycardia (≥ 100 bpm)
- Pre-existing severe musculoskeletal, neurological or psychiatric condition that may affect their ability to complete the testing battery or exercise training, as determined by the patient's physician
- Involvement in any other clinical trial or exercise trial
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Standard care
Standard care plus exercise
Arm Description
This group did not receive any supervised exercise or were not given any specific exercise recommendations during the trial period. However, patients in this group were offered the exercise intervention after completing the study.
This group received standard care in addition to a 3-month exercise intervention upon initiating androgen deprivation therapy.
Outcomes
Primary Outcome Measures
Whole body fat mass (kg)
Whole body fat mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This was chosen as the primary outcome because adiposity has shown a high propensity to increase during the initial phases of androgen deprivation therapy, more so than other measures (Galvao et al. 2011), which highlights the importance of targeting body fat at this stage of treatment.
Secondary Outcome Measures
Whole body fat mass (kg)
Whole body fat mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This was chosen as the primary outcome because adiposity has shown a high propensity to increase during the initial phases of androgen deprivation therapy, more so than other measures (Galvao et al. 2011), which highlights the importance of targeting body fat at this stage of treatment.
Whole body fat-free mass (kg)
Whole body fat-free mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This method is highly valid for measuring changes in body composition (Savastano et al. 2010).
Anthropometric measurements (cm)
Waist, hip, mid-upper arm, forearm, mid-thigh and calf circumferences were measured with a non-stretching tape using standard techniques.
Peak oxygen consumption (VO2peak, ml/kg/min)
Determined as the highest oxygen consumption (V̇O2) attained during the cardiopulmonary exercise test
Ventilatory anaerobic threshold (ml/kg/min)
Estimated using the modified V-slope method and confirmed by evaluating ventilatory equivalents and end-tidal pressures. Two analysts independently determined the ventilatory anaerobic threshold, with discrepancies of ≥ 7.5% resolved through discussion and consultation with a third analyst if necessary.
Ventilatory equivalents for O2 (V̇E/V̇O2) and CO2 (V̇E/V̇CO2)
Ratio of minute ventilation to O2 consumption and CO2 output at the ventilatory anaerobic threshold
Oxygen pulse (ml/beat)
Ratio of oxygen consumption to heart rate at peak exercise during the cardiopulmonary exercise test
Oxygen uptake efficiency slope (OUES)
Determined as the linear relationship between oxygen uptake and the logarithmic transformation of minute ventilation during the cardiopulmonary exercise test
Concentration of cholesterol (mmol/L)
Concentrations of total cholesterol, low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) were measured from venous blood.
Concentration of triglycerides (mmol/L)
The concentration of triglycerides was measured from venous blood.
Concentration of testosterone (nmol/L)
Concentration of total testosterone was measured from venous blood.
Concentration of sex hormone binding globulin (nmol/L)
Concentration of sex hormone binding globulin was measured from venous blood.
QRISK®2-2017 score
The percent risk of a cardiovascular disease event occurring in the next 10 years was calculated with QRISK®2-2017 Web Calculator (https://qrisk.org/2017). The total score ranges from 0 to 100 %, with higher scores indicating a greater risk of cardiovascular disease.
Gleason score
Gleason scores were measured from prostate biopsies. A score of 1 to 5 is assigned to the cells that make up the largest area of the tumor and another score of 1 to 5 is assigned to the cells that comprise the next largest area. A total Gleason score is then calculated by adding both of these scores together. Total scores ranged from 2 to 10, with 2 representing the most well-differentiated tumors and 10 the least-differentiated tumors.
Prostate specific antigen (ng/mL)
Concentration of prostate specific antigen was measured from venous blood.
Skinfold thickness (mm)
Skinfold thickness was measured at suprailiac and subscapular sites with a skinfold caliper (Harpenden Skinfold Caliper, Baty International, Sussex, UK).
Hand grip strength (kg)
Hand grip strength was measured with an analogue dynamometer (Takei Scientific Instruments Ltd., Tokyo, Japan).
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire (version 4)
Disease-specific health-related quality of life was assessed with the FACT-P 39-item questionnaire (version 4). Each item has a 5-point Likert-like response scale ranging from 0 ("Not at all") to 4 ("Very much"). A total score is calculated as the sum of each score from items 1 to 39, which can range from 0 to 156. Negatively worded items are reverse scored (subtracted from 4) prior to summing so that higher total scores indicate better health-related quality of life.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale (version 4)
Fatigue was assessed with the 13-item FACIT-Fatigue scale (version 4). Each item has a 5-point Likert-like response scale ranging from 0 ("Not at all") to 4 ("Very much"). A total score is calculated as the sum of each score from items 1 to 13, which can range from 0 to 52. Negatively worded items are reverse scored (subtracted from 4) prior to summing so that higher total scores indicate less experience of fatigue.
Godin Leisure-Time Exercise questionnaire
The Godin Leisure-Time Exercise questionnaire was used to characterise levels of physical activity. The questionnaire contains three items and asks the patient to recall the number of bouts of strenuous, moderate, or mild physical activity that exceed 15 min in duration in which they have engaged in over a typical week. A total score is calculated by multiplying the number of strenuous, moderate, and mild physical activity bouts by weights of 9, 5, and 3, respectively, and summing those values in an overall score that ranges from 0 to 119 in arbitrary units. Higher scores indicate participation in higher levels of physical activity.
Number of recruited participants
Measured as the number of eligible participants who were eligible and consented to participate in the trial. This will be reported in a Consolidated Standards of Reporting Trials (CONSORT) participant flowchart.
Number of adverse events
The number of adverse events were recorded to determine the feasibility of the exercise intervention. An adverse event was defined as the occurrence of any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the exercise intervention. The type of adverse events was also noted.
Attrition rate
Established as the number of patients in the experimental group who discontinued the exercise intervention
Number of patients who were lost to follow-up
In the experimental group, patients lost to follow-up were characterised as those who completed the exercise intervention but did not complete endpoint testing. In the control group, patients lost to follow-up were the number of patients who did not complete endpoint testing.
Average number of exercise sessions completed
The number of exercise sessions completed by each participant in the intervention group was recorded. These values were than averaged to provide a measure of adherence. The maximum number of exercise sessions that participants could complete was 24, so adherence ranged from 0 to 24 sessions, with higher scores indicating greater adherence.
Full Information
NCT ID
NCT03776045
First Posted
December 6, 2018
Last Updated
December 12, 2018
Sponsor
University of East Anglia
Collaborators
Norfolk and Norwich University Hospitals NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT03776045
Brief Title
PROState Cancer Patients Initiating Hormone Therapy: Effect of Exercise on CARDIOvascular Health (PROSCARDIO)
Acronym
PROSCARDIO
Official Title
Effects of Exercise in Prostate Cancer Patients Initiating Androgen Deprivation Therapy: A Randomised Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
August 12, 2013 (Actual)
Primary Completion Date
February 3, 2016 (Actual)
Study Completion Date
February 3, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of East Anglia
Collaborators
Norfolk and Norwich University Hospitals NHS Foundation Trust
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study evaluates whether exercise can reduce treatment-related adverse effects in prostate cancer patients initiating androgen deprivation therapy. Half of recruited participants completed a 3-month exercise intervention, while the other half did not perform any supervised exercise. It was anticipated that exercise would have a positive effect on body composition, cardiorespiratory fitness and quality of life.
Detailed Description
Androgen deprivation therapy (ADT) is routinely used as first-line treatment for locally advanced and metastatic prostate cancer. However, it is associated with many side effects such as increased fat mass and reduced skeletal muscle mass, cardiorespiratory fitness and metabolic health. Ultimately, these negative changes induced by ADT contribute to reduced health-related quality of life (HRQoL). This study evaluates whether 3-months of exercise can mitigate treatment toxicity in prostate cancer patients initiating ADT.
In a parallel groups, prospective, randomised controlled design, participants were randomly allocated to a standard care control group or standard care plus exercise group. The exercise group completed 3-months of combined aerobic and resistance training. The standard care group did not receive any supervised exercise or specific physical activity recommendations. Outcomes were assessed at baseline, 3-month (post-intervention), and 6-month (follow-up) endpoints.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate Cancer, Androgen deprivation therapy, Exercise
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
After baseline measures were collected, participants were randomly allocated (1:1) to standard care or standard care plus exercise using a randomisation sequence created by an independent researcher (nQuery, Statistical Solutions, USA). Treatment allocation was concealed from the research team until after baseline measurements were collected.
Masking
Outcomes Assessor
Masking Description
Outcome assessors and data analysts were blind to treatment allocation. It was not possible to blind participants or the intervention facilitator.
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard care
Arm Type
No Intervention
Arm Description
This group did not receive any supervised exercise or were not given any specific exercise recommendations during the trial period. However, patients in this group were offered the exercise intervention after completing the study.
Arm Title
Standard care plus exercise
Arm Type
Experimental
Arm Description
This group received standard care in addition to a 3-month exercise intervention upon initiating androgen deprivation therapy.
Intervention Type
Other
Intervention Name(s)
Standard care plus exercise
Intervention Description
The exercise was supervised by exercise science staff in the exercise science facilities at the University of East Anglia, UK. Participants competed two weekly sessions for 12 weeks upon initiating ADT. Each session lasted ~60 min and included aerobic interval exercise on a cycle ergometer (Monark 824E; Varberg, Sweden) followed by resistance training. In addition to the supervised exercise sessions, patients were advised on how to increase their habitual physical activity levels and were encouraged to engage in 30 minutes of self-directed exercise on three days each week (e.g. brisk walking, cycling, home-based resistance training).
Primary Outcome Measure Information:
Title
Whole body fat mass (kg)
Description
Whole body fat mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This was chosen as the primary outcome because adiposity has shown a high propensity to increase during the initial phases of androgen deprivation therapy, more so than other measures (Galvao et al. 2011), which highlights the importance of targeting body fat at this stage of treatment.
Time Frame
Adjusted mean difference between groups at 3-month endpoint
Secondary Outcome Measure Information:
Title
Whole body fat mass (kg)
Description
Whole body fat mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This was chosen as the primary outcome because adiposity has shown a high propensity to increase during the initial phases of androgen deprivation therapy, more so than other measures (Galvao et al. 2011), which highlights the importance of targeting body fat at this stage of treatment.
Time Frame
Adjusted mean difference between groups at 6-month endpoint
Title
Whole body fat-free mass (kg)
Description
Whole body fat-free mass was measured with bioelectrical impedance analysis (BIA) and concurrent bioelectrical impedance vector analysis (BIVA) with a single-frequency, phase-sensitive 50 kilohertz bioelectrical impedance analyzer (BIA-101, RJL/Akern Systems, Florence, Italy). This method is highly valid for measuring changes in body composition (Savastano et al. 2010).
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Anthropometric measurements (cm)
Description
Waist, hip, mid-upper arm, forearm, mid-thigh and calf circumferences were measured with a non-stretching tape using standard techniques.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Peak oxygen consumption (VO2peak, ml/kg/min)
Description
Determined as the highest oxygen consumption (V̇O2) attained during the cardiopulmonary exercise test
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Ventilatory anaerobic threshold (ml/kg/min)
Description
Estimated using the modified V-slope method and confirmed by evaluating ventilatory equivalents and end-tidal pressures. Two analysts independently determined the ventilatory anaerobic threshold, with discrepancies of ≥ 7.5% resolved through discussion and consultation with a third analyst if necessary.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Ventilatory equivalents for O2 (V̇E/V̇O2) and CO2 (V̇E/V̇CO2)
Description
Ratio of minute ventilation to O2 consumption and CO2 output at the ventilatory anaerobic threshold
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Oxygen pulse (ml/beat)
Description
Ratio of oxygen consumption to heart rate at peak exercise during the cardiopulmonary exercise test
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Oxygen uptake efficiency slope (OUES)
Description
Determined as the linear relationship between oxygen uptake and the logarithmic transformation of minute ventilation during the cardiopulmonary exercise test
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Concentration of cholesterol (mmol/L)
Description
Concentrations of total cholesterol, low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) were measured from venous blood.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Concentration of triglycerides (mmol/L)
Description
The concentration of triglycerides was measured from venous blood.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Concentration of testosterone (nmol/L)
Description
Concentration of total testosterone was measured from venous blood.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Concentration of sex hormone binding globulin (nmol/L)
Description
Concentration of sex hormone binding globulin was measured from venous blood.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
QRISK®2-2017 score
Description
The percent risk of a cardiovascular disease event occurring in the next 10 years was calculated with QRISK®2-2017 Web Calculator (https://qrisk.org/2017). The total score ranges from 0 to 100 %, with higher scores indicating a greater risk of cardiovascular disease.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Gleason score
Description
Gleason scores were measured from prostate biopsies. A score of 1 to 5 is assigned to the cells that make up the largest area of the tumor and another score of 1 to 5 is assigned to the cells that comprise the next largest area. A total Gleason score is then calculated by adding both of these scores together. Total scores ranged from 2 to 10, with 2 representing the most well-differentiated tumors and 10 the least-differentiated tumors.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Prostate specific antigen (ng/mL)
Description
Concentration of prostate specific antigen was measured from venous blood.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Skinfold thickness (mm)
Description
Skinfold thickness was measured at suprailiac and subscapular sites with a skinfold caliper (Harpenden Skinfold Caliper, Baty International, Sussex, UK).
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Hand grip strength (kg)
Description
Hand grip strength was measured with an analogue dynamometer (Takei Scientific Instruments Ltd., Tokyo, Japan).
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire (version 4)
Description
Disease-specific health-related quality of life was assessed with the FACT-P 39-item questionnaire (version 4). Each item has a 5-point Likert-like response scale ranging from 0 ("Not at all") to 4 ("Very much"). A total score is calculated as the sum of each score from items 1 to 39, which can range from 0 to 156. Negatively worded items are reverse scored (subtracted from 4) prior to summing so that higher total scores indicate better health-related quality of life.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale (version 4)
Description
Fatigue was assessed with the 13-item FACIT-Fatigue scale (version 4). Each item has a 5-point Likert-like response scale ranging from 0 ("Not at all") to 4 ("Very much"). A total score is calculated as the sum of each score from items 1 to 13, which can range from 0 to 52. Negatively worded items are reverse scored (subtracted from 4) prior to summing so that higher total scores indicate less experience of fatigue.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Godin Leisure-Time Exercise questionnaire
Description
The Godin Leisure-Time Exercise questionnaire was used to characterise levels of physical activity. The questionnaire contains three items and asks the patient to recall the number of bouts of strenuous, moderate, or mild physical activity that exceed 15 min in duration in which they have engaged in over a typical week. A total score is calculated by multiplying the number of strenuous, moderate, and mild physical activity bouts by weights of 9, 5, and 3, respectively, and summing those values in an overall score that ranges from 0 to 119 in arbitrary units. Higher scores indicate participation in higher levels of physical activity.
Time Frame
Adjusted mean difference between groups at 3-month and 6-month endpoints
Title
Number of recruited participants
Description
Measured as the number of eligible participants who were eligible and consented to participate in the trial. This will be reported in a Consolidated Standards of Reporting Trials (CONSORT) participant flowchart.
Time Frame
Descriptive statistics reported during the two-year recruitment period
Title
Number of adverse events
Description
The number of adverse events were recorded to determine the feasibility of the exercise intervention. An adverse event was defined as the occurrence of any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the exercise intervention. The type of adverse events was also noted.
Time Frame
Descriptive statistics reported during the 3-month intervention period
Title
Attrition rate
Description
Established as the number of patients in the experimental group who discontinued the exercise intervention
Time Frame
Descriptive statistics reported during the 3-month intervention period.
Title
Number of patients who were lost to follow-up
Description
In the experimental group, patients lost to follow-up were characterised as those who completed the exercise intervention but did not complete endpoint testing. In the control group, patients lost to follow-up were the number of patients who did not complete endpoint testing.
Time Frame
Descriptive statistics reported at 3-month and 6-month endpoints
Title
Average number of exercise sessions completed
Description
The number of exercise sessions completed by each participant in the intervention group was recorded. These values were than averaged to provide a measure of adherence. The maximum number of exercise sessions that participants could complete was 24, so adherence ranged from 0 to 24 sessions, with higher scores indicating greater adherence.
Time Frame
Descriptive statistics reported during the 3-month intervention period
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male
Aged 50 to 80 years
Histologically confirmed stage I-IV prostate cancer
Scheduled for treatment with a luteinizing hormone-releasing hormone (LHRH) agonist either alone or combined with radiotherapy
Anticipated to remain on androgen deprivation therapy (ADT) for at least the next 6 months
Willing and able to give written informed consent.
Understand written and verbal instructions in English
World Health Organisation (WHO) performance status 0 to 1
Exclusion Criteria:
Previously treated with ADT
Diagnosed or suspected metastatic bone disease
Absolute contraindications to exercise testing and training as defined by the American College of Sports Medicine (ACSM, 2010)
Prior myocardial infarction or heart failure
Chronic obstructive pulmonary disease (COPD)
Poorly controlled hypertension (≥ 200/110 mmHg)
Uncontrolled supraventricular tachycardia (≥ 100 bpm)
Pre-existing severe musculoskeletal, neurological or psychiatric condition that may affect their ability to complete the testing battery or exercise training, as determined by the patient's physician
Involvement in any other clinical trial or exercise trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Saxton, Saxton
Organizational Affiliation
Northumbria University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Wilphard Ndjavera, MD
Organizational Affiliation
Norfolk and Norwich University Hospitals NHS Foundation Trust
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21849187
Citation
Galvao DA, Taaffe DR, Spry N, Joseph D, Newton RU. Acute versus chronic exposure to androgen suppression for prostate cancer: impact on the exercise response. J Urol. 2011 Oct;186(4):1291-7. doi: 10.1016/j.juro.2011.05.055. Epub 2011 Aug 17.
Results Reference
background
PubMed Identifier
19862582
Citation
Savastano S, Belfiore A, Di Somma C, Mauriello C, Rossi A, Pizza G, De Rosa A, Prestieri G, Angrisani L, Colao A. Validity of bioelectrical impedance analysis to estimate body composition changes after bariatric surgery in premenopausal morbidly women. Obes Surg. 2010 Mar;20(3):332-9. doi: 10.1007/s11695-009-0006-5. Epub 2009 Oct 28.
Results Reference
background
Learn more about this trial
PROState Cancer Patients Initiating Hormone Therapy: Effect of Exercise on CARDIOvascular Health (PROSCARDIO)
We'll reach out to this number within 24 hrs