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

Trial Summary

What is the purpose of this trial?

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 prostate cancer progression. The main question it aims to answer is if this treatment will help maintain muscle mass to help in reducing fatigue and improving physical function, independence, and quality of life. Participants will be asked to participate in a 52-week exercise intervention consisting of a twice weekly telehealth resistance training program.

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 creatine supplementation safe for humans?

Creatine monohydrate is generally considered safe for humans when taken at recommended doses, with common side effects being mild, such as temporary water retention. Studies have shown no serious adverse effects, and a daily intake of 3 grams is unlikely to pose safety concerns for healthy adults, though caution is advised for certain forms like creatine orotate and creatine phosphate. ^{1 2 3 4 5}

How does the creatine monohydrate treatment differ from other prostate cancer treatments?

Creatine monohydrate combined with resistance training is unique because it focuses on enhancing muscle strength and energy levels, which may help improve quality of life for prostate cancer patients, especially those undergoing home-based telehealth programs. Unlike standard treatments like chemotherapy or immunotherapy, this approach is non-invasive and can be administered at home, potentially offering a supportive role alongside traditional therapies. ^{6 7 8 9 10}

Research Team

Adriana Coletta

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 (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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Creatine and creatine forms intended for sports nutrition. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Creatine supplementation. [2016]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Bioavailability, Efficacy, Safety, and Regulatory Status of Creatine and Related Compounds: A Critical Review. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Risk assessment for creatine monohydrate. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Prostate cancer vaccines: Update on clinical development. [2022]

7. England pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Has the Landscape of Immunotherapy for Prostate Cancer Changed? A Systematic Review and Post Hoc Analysis. [2023]

9. United States 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. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Emerging Immunotargets and Immunotherapies in Prostate Cancer. [2019]