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.

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 markers of the immune system and allostatic load).

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.

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 Creatine 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).