Creatine + Resistance Training for Prostate Cancer

(CREATINE-52 Trial)

Overseen By Susan Sharry

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: University of Utah

Must be taking: GnRH agonists/antagonists, ARPI

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Low eGFR, ECOG ≥ 3, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether creatine supplements combined with resistance training can help maintain muscle mass in men with prostate cancer. Researchers aim to determine if this approach can reduce fatigue and enhance physical abilities, independence, and overall quality of life. Participants will perform resistance exercises twice a week at home through a telehealth program. Men with prostate cancer that hasn't progressed on current hormone therapy and who are not already engaged in regular resistance training might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop your current medications. However, you must be on a stable regimen of certain prostate cancer treatments for at least 12 weeks before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that creatine monohydrate was safe and well-tolerated when combined with strength training for prostate cancer patients. Research shows that creatine does not add extra risk for patients already undergoing cancer treatments like hormone therapy. Patients did not experience more side effects when taking creatine compared to those who did not.

Additionally, creatine is a common supplement used to build muscle and improve strength. It is generally considered safe for most people. While creatine does not appear to increase the risk of prostate cancer progression, it might help maintain muscle mass, which is important for reducing fatigue and improving physical ability in patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about this treatment for prostate cancer because it combines creatine monohydrate with resistance training, all delivered through a convenient home-based telehealth platform. Unlike standard treatments that often involve medications or invasive procedures, this approach harnesses the natural benefits of creatine, a compound known for enhancing muscle strength and recovery. The use of telehealth makes it accessible and less burdensome for patients, allowing them to engage in beneficial exercise routines without frequent hospital visits. This innovative combination could offer a supportive therapy that improves quality of life and potentially enhances treatment outcomes.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that combining creatine monohydrate with strength training can help maintain muscle mass in people with prostate cancer. This trial will test this combination in one of its arms, where participants will receive home-based, telehealth resistance training with creatine monohydrate supplementation. This combination has lowered levels of substances in the body that cause inflammation, which are linked to severe muscle loss. Some studies suggest that this approach may also reduce tiredness and improve overall physical ability. For those receiving hormone therapy, strength training and creatine can help prevent weight gain. While not all studies agree, many suggest that using creatine with exercise could be a promising way to keep muscles strong and improve quality of life. ^{1 2 6 7 8}

Who Is on the Research Team?

Adriana Coletta

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

Men over 18 with metastatic prostate cancer not currently progressing on therapy can join. They must be undergoing hormone treatments, have internet access for video calls, and be willing to do a home-based exercise program and take creatine or placebo as assigned.

Inclusion Criteria

You are capable of granting consent and prepared to sign a legally compliant authorization document.

My prostate cancer has spread, but my current treatment is still working.

I am willing to send weekly updates on my supplement use during the study.

Exclusion Criteria

I need help with my daily activities due to my health condition.

My kidney function is severely reduced.

I am currently undergoing or may need radiation therapy during the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 52 weeks of home-based, telehealth resistance training with creatine monohydrate supplementation or placebo

52 weeks

Twice weekly telehealth sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Creatine Monohydrate
• Home-based, telehealth

Trial Overview The trial is testing if creatine supplements combined with resistance training at home can help maintain muscle mass and slow down prostate cancer progression over a year-long period compared to a placebo group.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 2 Interventions

Home-based, telehealth resistance training (RT) with creatine monohydrate supplementation (Cr)

Group II: Arm 2 Placebo Group 2 Interventions

Home-based, telehealth resistance training (RT) with placebo (PLA)

Creatine Monohydrate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Approved in European Union as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Approved in Canada as Creatine Monohydrate for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Sipuleucel-T, an autologous cellular vaccine, significantly improved median overall survival in men with metastatic, castration-resistant prostate cancer (CRPC) to 25.8 months compared to 21.7 months for placebo, marking it as the first therapeutic cancer vaccine approved in the USA.

Other immunotherapy approaches, such as PROSTVAC and T-cell modulation strategies like ipilimumab, show promise but require further research to enhance their effectiveness and clinical benefits in treating CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of immunotherapy in prostate cancer. Gerritsen, WR.[2022]

Creatine monohydrate effectively enhances muscle performance during short-duration, high-intensity exercises, with a recommended loading dose of 0.3 g·kg·d for 5 to 7 days followed by a maintenance dose of 0.03 g·kg·d for 4 to 6 weeks, although loading is not strictly necessary.

Creatine is generally safe with few side effects, primarily causing transient water retention; however, there are concerns about potential liver and kidney complications when taken in high doses or combined with other supplements over extended periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine supplementation. Hall, M., Trojian, TH.[2016]

Creatine monohydrate is effective for enhancing performance in high-intensity, short-duration activities, supported by a large body of research involving both acute (20 g/d) and chronic (3-5 g/d) supplementation studies.

The Observed Safe Level (OSL) for chronic creatine supplementation is established at 5 g/d, indicating strong safety evidence at this dosage, while higher intakes lack sufficient long-term safety data despite being tested without adverse effects in acute studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. Shao, A., Hathcock, JN.[2013]

This systematic review analyzed 24 prostate cancer patients and found that immunotherapies, particularly IMM-101, showed promising results with a mean overall survival (OS) of 56 months, indicating potential benefits for patients.

Among the immunotherapies studied, Pembrolizumab and IMM-101 were the most commonly used, highlighting their relevance in the treatment landscape for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. Ashraf, MU., Farwa, U., Siddiqa, M., et al.[2023]

Enzalutamide, when combined with a Twist-targeting immunotherapy, significantly improved overall survival in a mouse model of castration-resistant prostate cancer (CRPC), extending survival from 10.3 weeks to 27.5 weeks.

The study found that enzalutamide did not impair the immune response generated by the Twist vaccine, suggesting that this combination therapy could be a safe and effective strategy for treating advanced-stage prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. Ardiani, A., Farsaci, B., Rogers, CJ., et al.[2021]

Creatine monohydrate (CrM) remains the only form of creatine with substantial evidence supporting its bioavailability, efficacy, and safety, as confirmed by a review of various marketed creatine forms.

Despite ongoing claims about other 'novel forms' of creatine, many lack sufficient evidence for effectiveness and safety, and CrM is still the recommended source by professional organizations and regulatory authorities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. Kreider, RB., Jäger, R., Purpura, M.[2022]

Clinical trials over the past 12 years indicate that vaccines for castration-resistant prostate cancer (CRPC) are safe and can stimulate immune responses specifically targeting prostate cancer cells.

These vaccines show promise as potential alternative or complementary therapies to the current standard treatment of docetaxel plus prednisone, suggesting a new avenue for managing metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate cancer vaccines: Update on clinical development. Geary, SM., Salem, AK.[2022]

Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 agents, are promising new treatments for prostate cancer, targeting both innate and adaptive immune responses.

Combining these immunotherapies with standard treatments like anti-androgen therapy, chemotherapy, or radiation may enhance their effectiveness in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Immunotargets and Immunotherapies in Prostate Cancer. Montironi, R., Santoni, M., Sotte, V., et al.[2019]

Creatine monohydrate is generally considered safe for healthy adults at a daily intake of 3 grams, with some minor side effects like gastrointestinal issues and muscle cramps reported.

While most creatine forms are unlikely to pose safety concerns, there are specific safety concerns associated with creatine orotate, creatine phosphate, and magnesium creatine chelate, indicating that not all creatine supplements are equally safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. Andres, S., Ziegenhagen, R., Trefflich, I., et al.[2018]

A systematic review of 29 studies involving 951 female participants found no serious adverse outcomes or deaths associated with creatine monohydrate (CrM) supplementation, indicating it is safe for use in women.

There were no significant differences in total adverse events, gastrointestinal issues, or weight gain between those taking CrM and those not, suggesting that CrM does not increase the risk of these complications in females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. de Guingand, DL., Palmer, KR., Snow, RJ., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11025211/

Creatine supplementation and resistance training to ... Creatine monohydrate supplementation also reduces levels of inflammatory markers associated with severe muscle loss [6]. In addition, creatine ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1440244024005152

Creatine supplementation does not add to resistance ... Increases in fat mass during androgen deprivation therapy for prostate cancer appear to be mitigated with resistance training and creatine supplementation. 1.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39366880/

Creatine supplementation does not add to resistance ... Creatine supplementation does not add to resistance training effects in prostate cancer patients under androgen deprivation therapy: A double-blind randomized ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-09483

Creatine Supplementation in Combination with Resistance ... Combining creatine supplementation with resistance training may be more effective at preserving muscle mass and improving other health-related outcomes (fatigue ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06112990/creatine-supplementation-and-resistance-training-to-preserve-muscle-mass-and-attenuate-cancer-progression

Creatine Supplementation and Resistance Training to ... The goal of this clinical trial is to test the use of creatine monohydrate supplementation with resistance training to preserve muscle mass and help lessen ...

6. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1460057/full

The association between dietary creatine intake and ... For each standard deviation (SD) increase in dietary creatine intake, cancer risk decreased by 5% (adjusted odds ratio (OR) = 0.95, 95% CI: 0. ...

7. aacrjournals.org aacrjournals.org/cancerres/article/82/14/2565/706947/Cyclocreatine-Suppresses-Creatine-Metabolism-and

Cyclocreatine Suppresses Creatine Metabolism and Impairs ... Our data point to creatine uptake as a vulnerability of progressive prostate cancer. This is of particular relevance given that dietary creatine ...

8. news-medical.net news-medical.net/news/20231011/Clinical-trial-tests-creatine-monohydrate-and-exercise-to-preserve-muscle-mass-in-prostate-cancer-patients.aspx

Clinical trial tests creatine monohydrate and exercise to ... Clinical trial tests creatine monohydrate and exercise to preserve muscle mass in prostate cancer patients.