A Comparison of Aerobic and Resistance Exercise to Counteract Treatment Side Effects in Men With Prostate Cancer

Study Overview
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Brief Summary
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Prostate cancer is the second most common cancer in men. Those in the intermediate/high-risk categories typically receive androgen deprivation therapy (ADT) and radiotherapy. ADT greatly reduces androgen production as prostate cancer is dependent on testosterone and dihydrotestosterone for its growth.The side effects of ADT therapy are extensive and include changes in body composition (muscle loss, bone loss and fat gain), strength, mood, physical function, sexual function and increased cardiovascular risk and fatigue. Many of these side effects can be influenced by exercise training, both resistance training and aerobic training. However, the most appropriate exercise regime for men undergoing ADT has received little research attention.

Detailed Description
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Although many interventions for prostate survivors emphasise resistance exercise to maintain muscle mass and strength. Arguments could equally be made for programmes emphasising aerobic exercise for fatigue, anxiety, cardiovascular risk reduction and indeed overall survival. Comparisons of programmes that emphasise each exercise mode are clearly required. Therefore the overall purpose of this feasibility and pilot randomised control trial is to determine the feasibility and preliminary effectiveness of an aerobic emphasised exercise program (AE) verses a resistance emphasise exercise program (RE) in a rehabilitation setting, over 6 months, for prostate cancer men undergoing Androgen Deprivation Therapy (ADT).

Official Title
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A Comparison of Aerobic and Resistance Exercise for Counteracting the Adverse Effects of Androgen Deprivation Therapy in Men With Prostate Cancer

Conditions
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Exercise, Prostate Cancer

Intervention / Treatment
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* Other: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >18 years of age with a histologically diagnosed prostate cancer Prescribed ADT (Androgen deprivation Therapy) Self-reported not to be partaking in regular exercise (structured aerobic or resistance training ≥ 2 sessions/week) in the past 3 months. Medically cleared to exercise by their oncologist Exclusion Criteria: Prior exposure to ADT >12 months Prior hypogonadism Established metastatic bone disease Established Osteoporosis Musculoskeletal/Cardiovascular and/or Neurological disease that could put them at risk from exercise as judged by the attending physician.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot randomised control trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Emphasised Exercise Intervention<br>The intervention will comprise of 24 weeks of twice weekly supervised exercise sessions, emphasising aerobic exercise. To reflect a real-world setting, each group will experience both aerobic and resistance exercise, but there will be a 75%:25% predominant: subsidiary mode emphasis based on exercise duration within each session. | Other: Exercise<br>* An individualised, progressive and autoregulated exercise programme, supervised by a trained professional.<br>|
| Experimental: Resistance Emphasised Exercise Intervention<br>The intervention will comprise of 24 weeks of twice weekly supervised exercise sessions, emphasising resistance exercise. To reflect a real-world setting, each group will experience both aerobic and resistance exercise, but there will be a 75%:25% predominant: subsidiary mode emphasis based on exercise duration of exercise within each session. | Other: Exercise<br>* An individualised, progressive and autoregulated exercise programme, supervised by a trained professional.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility- recruitment rate (%) | The recruitment rate will be established by comparing the number of potential participants approached and how many agreed to participate in the trial. This will be reported in percentage format. | At study conclusion | 
| Feasibility- retention rate (%) | Percentage of participants that completed the 24 week intervention compared to the number of participants randomised. This will be reported in percentage format. | Intervention conclusion 24 weeks | 
| Feasibility- exercise program adherence through attendance %. | The research team will report adherence to the exercise program through attendance of supervised classes. Attendance will be reported as a percentage. | Throughout 24 week intervention | 
| Feasibility- exercise prescription adherence (% of modified sessions compared to attended exercise sessions) | The research team will report adherence to the exercise prescription by reporting the number of modified sessions compared to attended exercise sessions. This will be reported as a percentage. | Throughout 24 week intervention | 
| Feasibility- Adverse Event using CTCAE v4.0 grading system. | The research team will report any adverse events in general or in relation to the exercise program using CTCAE v4.0 grading system. | At study conclusion | 
| Feasibility- Patient satisfaction/acceptability through qualitative evaluation. | Determined by qualitative evaluation, using semi structured interviews and exit surveys to evaluate the acceptability, experiences and feasibility of the intervention. | Following intervention conclusion at 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General quality of life by questionnaire | The RAND 36-Item Health Survey comprises of 36 questions and assesses eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scores range from 0-100. A higher score indicates a high quality of life and a favourable health status. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Cancer Specific quality of life by questionnaire | The European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) comprises of 30 questions, categorised into five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. The remaining six single-item (dyspnoea, appetite loss, sleep disturbance, constipation, diarrhoea and the financial impact) scales assess symptoms. Scores range from 0-100. A higher score for the functional scales and global health status indicates better functioning and quality of life. A higher score on the symptom and single-item scales denotes a high level of symptoms (i.e. a poor quality of life). | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Prostate cancer specific quality of life by questionnaire | The European Organisation for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-PR25) is a prostate cancer supplementary questionnaire module to be employed in conjunction with EORTC QLQ-C30. It comprises of five multi-item scales to assess sexual activity, sexual functioning, urinary symptoms, bowel symptoms and hormonal treatment-related symptoms and one single item assessing incontinence. Scores range from 0-100. A high score for the sexual activity and sexual functioning scales represents a high level of functioning. A high score for urinary, bowel and hormonal treatment related symptoms scales and incontinence aid item represents a high level of symptomatology. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Fatigue by questionnaire | The Functional Assessment of Cancer Therapy - Fatigue (FACIT-Fatigue) questionnaire will be used to measure fatigue. Patients will score 13 fatigue items over the past 7 days on a scale (0 = not at all; 4 = very much), generating a total (0 - 52). A higher score indicates lower levels of fatigue. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Physical Activity (subjective) by questionnaire | The Godin Leisure Time Exercise questionnaire will be used to calculate the average amount of strenuous, moderate and light exercise a participant performs in a typical 7 day period. A score of 24 units or more indicates the participant is active, 14-23 units indicates moderately active and less than 14 units suggests the participant is insufficiently active/sedentary. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Anthropometric assessment. | Height will be measured in cm and body weight in kg, which will be combined to report BMI in kg/m(squared). | At baseline and 24 weeks (end of intervention) | 
| Waist and Hip circumference analysis (cms) | Waist circumference and hip circumference will be measured in centimetres. These two measurements will be used to calculate the participants waist: hip ratio. All measurements will be taken in duplication and averaged before data entry. If there is a substantial difference between the two measures, a third measurement will be taken. | At baseline and 24 weeks (end of intervention) | 
| Body composition (fat mass) analysis using Dual Energy X Ray Absorptiometry (Dexa) | Fat mass (grams and percentage) will be assessed using DEXA (Horizon W, Hologic, 304492M). Participants will be scanned after an overnight fast and will be instructed to regulate their water/fluid intake in the days leading up to the scan, so they are adequately hydrated. All scans will be completed at the same time as much as possible to account for physiological changes in body composition throughout the day. | At baseline and 24 weeks (end of intervention) | 
| Body composition (fat and lean mass) analysis using Dual Energy X Ray Absorptiometry (Dexa) | Lean mass (grams and percentage) will be assessed using DEXA (Horizon W, Hologic, 304492M). Participants will be scanned after an overnight fast and will be instructed to regulate their water/fluid intake in the days leading up to the scan, so they are adequately hydrated. All scans will be completed at the same time as much as possible to account for physiological changes in body composition throughout the day. | At baseline and 24 weeks (end of intervention) | 
| Bone density (BMD) measurement | Whole body bone Density will be measured using DEXA (Horizon W, Hologic, 304492M). BMD will be measured in g/cm(squared) and used to calculate a T-score (SD). A T-score shows how much a participant's BMD is higher or lower than the BMD of a healthy 30 year old adult and is the score most commonly used to diagnose low BMD. | At baseline and 24 weeks (end of intervention) | 
| Visceral fat area (VAT Area) in cm(squared) | Visceral fat area will be assessed using DEXA (Horizon W, Hologic, 304492M). It will be measured in cm(squared). Participants will be scanned after an overnight fast and will be instructed to regulate their water/fluid intake in the days leading up to the scan, so they are adequately hydrated. All scans will be completed at the same time as much as possible to account for physiological changes in body composition throughout the day | At baseline and 24 weeks (end of intervention) | 
| Atrial stiffness measured by a Pulse Wave Velocity Assessment (m/s) | A carotid-femoral pulse wave velocity test will be performed to assess arterial stiffness. It will be measured in meters per seconds (m/s). This will be performed as per manufactural instructions using a Complior, Alam medical device. Measurements will be taken in duplicate and the mean recorded, with a third measurement taken if difference between the two measurements is more than 0.5 m/s and median recorded. | At baseline and 24 weeks (end of intervention) | 
| Blood pressure (mmHg) | Blood pressure (diastolic and systolic) measured at rest. Blood pressure will be taken according to the American Heart Association's (AHA) guidelines. At least two readings and the average recorded. Additional readings will be taken if the difference between the two reading exceeds 5mm Hg. | At baseline and 24 weeks (end of intervention) | 
| Cardiovascular Fitness | Cardiovascular fitness will be determined by a submaximal incremental treadmill test using a modified Bruce protocol. The test will be scored by the time (minutes and seconds) taken to test completion. A longer time to completion means superior cardiovascular fitness. | 0(baseline), 8 weeks and 6 months (end of intervention) | 
| Peak torque/power for knee extension and flexion | An isokinetic dynamometry for knee extension and flexion will also be performed on a Biodex (Advantage BX™ Software Update v5.3.00) to measure peak torque (n.M) and power, using a similar protocol as previously used in cancer patients. | At baseline and 24 weeks (end of intervention) | 
| Lower limb strength [Leg Press] | Leg press 1 repetition maximum will be measured in kilograms (kg). A 1 repetition maximum is defined as the highest load that can be lifted through full range of movement for one time. | At baseline and 24 weeks (end of intervention) | 
| Upper limb strength [Chest Press] | Chest press 1 repetition maximum will be measured in kilograms (kg). A 1 repetition maximum is defined as the highest load that can be lifted through full range of movement for one time. | At baseline and 24 weeks (end of intervention) | 
| Functional Ability Assessment (Timed up and go) | The timed up and go assess the time (in seconds) it takes for a person to rise from a chair, walk three meters, turn around 180 degrees, walk back to the chair, and sit down while turning 180 degrees. It assesses mobility, balance, walking ability and falls risk in older adults. A lower score indicates better physical function. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Functional Ability Assessment (Sit to stand) | Sit to stand assesses the maximal repetitions a participant can stand up from a chair in 30 seconds. A higher score indicates better physical function. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Functional Ability Assessment (Grip test) | A hand-held dynamometry will be used to measure grip strength for each arm. this is a measure of upper body strength and a higher score suggests better upper body strength | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Functional Ability Assessment (Bess Balance test) | The Balance Error Scoring System is an objective measure of assessing static postural stability. A lower score= better balance and reduced falls risk. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Functional Ability Assessment (6 minute walk test) | A 6-min walk test measured the maximal meters walked in six minutes. A higher score indicated superior aerobic endurance and capacity. | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Functional Ability Assessment (Sit and reach) | The sit and reach test measures linear flexibility. The score is the most distant point (cm) reached with the fingertips. A higher score indicates better flexibility | At baseline, 8 weeks and 24 weeks (end of intervention) | 
| Biomarker Analysis: Blood lipids (mmol/L) | Blood lipids (total cholesterol, triglycerides, LDH and HDL) will be analysed Fasting blood will be taken from all participants using a standard venipuncture technique. All bloods will be analyzed in a certified clinical lab. | At baseline and 24 weeks (end of intervention) | 
| Biomarker Analysis: Glucose (mmol/L) | Fasted blood will be used to measure blood glucose (mmol/L), | At baseline and 24 weeks (end of intervention) | 
| Biomarker Analysis: Insulin (mIU/L) | Fasted blood will be used to measure blood insulin (mIU/L) | At baseline and 24 weeks (end of intervention) | 
| Biomarker Analysis: C-Reactive Protein (CRP) | Fasted blood will be used to measure C-reactive protein (mg/dL). | At baseline and 24 weeks (end of intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physical Fitness, Cancer, Prostate Cancer, Androgen Deprivation Therapy, Exercise