Resistance Training +/- Creatine for Metastatic Prostate Cancer Patients

Study Overview
=================
Brief Summary
-----------------
This trial studies how well resistance training with or without creatine monohydrate supplement works in improving body composition and health outcomes in patients with prostate cancer that has spread to other places in the body. Resistance training, with or without creatine monohydrate supplement, may help to improve feelings of tiredness and overall physical function in patients with prostate cancer.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate the change in lean mass with 12 weeks of creatine supplementation + resistance training compared to resistance training alone. SECONDARY OBJECTIVES: I. To evaluate change in other body composition variables (i.e. fat mass, fat-free mass, percent body fat, appendicular lean mass) with 12 weeks of creatine supplementation + resistance training compared to resistance training alone. II. To evaluate the change in health outcomes associated with body composition (i.e. physical function, fatigue, insulin regulation) with 12 weeks of creatine supplementation + resistance training compared to resistance training alone. III. To examine associations between creatine supplementation use and changes in biomarkers linked with prostate cancer progression (prostate specific antigen [PSA] and inflammatory markers). IV. To evaluate the degree of adherence to the creatine supplementation protocol. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients complete Personal Optimism with Exercise Recovery (POWER) resistance training program sessions twice weekly over 30-60 minute each for 12 weeks. GROUP II: Patients complete POWER resistance training program sessions twice weekly over 30-60 minutes each for 12 weeks and receive creatine monohydrate supplementation orally (PO) 4 times daily during week 1, and then once daily (QD) during weeks 2-12.

Official Title
-----------------
Creatine Supplementation With Resistance Training: A Novel Approach to Improving Body Composition and Associated Health Outcomes Among Prostate Cancer Patients

Conditions
-----------------
Fatigue, Metastatic Prostate Carcinoma, Sedentary Lifestyle, Stage IV Prostate Cancer AJCC (American Joint Committee on Cancer) v8, Stage IVA Prostate Cancer AJCC (American Joint Committee on Cancer) v8, Stage IVB Prostate Cancer AJCC (American Joint Committee on Cancer) v8

Intervention / Treatment
-----------------
* Dietary Supplement: Creatine Monohydrate
* Behavioral: Exercise Intervention
* Other: Questionnaire Administration


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Metastatic prostate cancer patients who have not met criteria for disease progression on ongoing systemic therapy. Currently treated with CYP17A1 inhibitors, surgical castration or medical castration with GnRH (gonadotropin-releasing hormone) agonists/antagonists, or androgen receptor blockers. Must have started the current regimen at least 12 weeks prior to enrollment. Confirmation by the patient's treating oncologist that the patient is able to start the exercise program. Regular access to an electronic device with internet service and ability for video calls (i.e. computer, smart phone, ipad, tablet, etc). Access to an active MyChart account or the willingness to create an account for the purposes of the trial. Must be able to read and understand English. Willingness to engage in a home-based resistance exercise program two days per week. If randomized to the creatine + resistance training group, willingness to take creatine monohydrate supplementation for the duration of the 12 week trial and avoid taking additional creatine-containing supplementation or other supplementation during the study period. If randomized to the resistance training group without creatine supplementation, willingness to avoid taking creatine monohydrate supplementation or additional creatine-containing supplementation or other supplementation during the study period. For participants randomized to the creatine arm willingness to complete and submit Weekly Creatinine Supplementation logs to study personnel via email, fax, or in person. Willingness to complete two assessment sessions (baseline and end-of-study). Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: Treatment with cytotoxic chemotherapy within 12 weeks prior to enrollment. Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m^2. Metastatic disease that, in the opinion of the treating oncologist, may obstruct compliant participation in the exercise program (i.e. extensive bone disease). Current or planned treatment with radiation therapy. *Subjects who may later require radiation therapy for their health and wellbeing during the course of the trial may be allowed to continue on trial, pending consultation with the PI, treating oncologist, and medical monitor (and DSMC as applicable).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I (resistance training)<br>Patients complete POWER resistance training program sessions twice weekly over 30-60 minute each for 12 weeks. | Behavioral: Exercise Intervention<br>* Complete POWER resistance training program<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Group II (resistance training, creatine supplementation)<br>Patients complete POWER resistance training program sessions twice weekly over 30-60 minutes each for 12 weeks and receive creatine monohydrate supplementation given orally 4 times daily during week 1, and then QD (once per day) during weeks 2-12. | Dietary Supplement: Creatine Monohydrate<br>* Given orally<br>* Other names: Creatine Supplement;Behavioral: Exercise Intervention<br>* Complete POWER resistance training program<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in lean mass | Assessed by whole-body dual x-ray absorptiometry (DXA) scan. | Baseline to 12 weeks post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fat mass | Assess body composition by whole-body DXA (dual x-ray absorptiometry) scan. | Baseline to 12 weeks post intervention | 
| Change in fat-free mass | Assess body composition by whole-body DXA (dual x-ray absorptiometry) scan. | Baseline to 12 weeks post intervention | 
| Change in percent body fat | Assess body composition by whole-body DXA (dual x-ray absorptiometry) scan. | Baseline to 12 weeks post intervention | 
| Change in appendicular lean mass | Assess body composition by whole-body DXA (dual x-ray absorptiometry) scan. | Baseline to 12 weeks post intervention | 
| Change in physical function | Assessed by physical performance battery testing | Baseline to 12 weeks post intervention | 
| Change in fatigue | Assessed by Functional Assessment of Chronic Illness Therapy Fatigue (FACIT Fatigue Scale, version 4) questionnaire which is a patient-reported measurement of change in fatigue. Level of fatigue is rated from 0 (not at all) to 4 (very much). FACIT-Fatigue Subscale Scoring Guidelines (Version 4) Record answers in item response column. If missing, mark with an X Perform reversals as indicated, and sum individual items to obtain a score. Multiply the sum of the item scores by the number of items in the subscale, then divide by the number of items answered. This produces the subscale score. The higher the score, the better the QOL. | Baseline to 12 weeks post intervention | 
| Change in insulin regulation | Assessed by Homeostatic Model Assessment of Insulin Resistance assessment. | Baseline to 12 weeks post intervention | 
| Change in serum PSA (prostate specific antigen) | Assessed by PSA lab | Baseline to 12 weeks post intervention | 
| Total percent of creatine supplementation consumed at end of study | Assessed by submission of supplementation logs and research pharmacy measurements of remaining creatine in the supplementation containers that will be returned by patients at the end-of-study assessment session. Pharmacy creatine measurements will be documented in Vestigo. | Baseline up to 12 weeks post intervention | 
| Change in inflammatory marker interleukin 6 (IL-6) | Assessed by serum testing of inflammatory marker | Baseline to 12 weeks post intervention | 
| Change in inflammatory marker interleukin 8 (IL-8) | Assessed by serum testing of inflammatory marker | Baseline to 12 weeks post intervention | 
| Change in inflammatory marker interleukin 10 (IL-10) | Assessed by serum testing of inflammatory marker | Baseline to 12 weeks post intervention | 
| Change in inflammatory marker tumor necrosis factor alpha (TNF-a) | Assessed by serum testing of inflammatory marker | Baseline to 12 weeks post intervention | 
| Change in serum glucose | Assessed by serum glucose testing | Baseline to 12 weeks post intervention |