Turmeric + Metformin for Prostate Cancer

Overseen By Madison Trujillo

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of Arkansas

Must be taking: iADT

Must not be taking: Carbonic anhydrase inhibitors

Disqualifiers: CLL, MGUS, RCC, liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 27

Duration: 8 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to assess the feasibility of adding a combination of metformin and turmeric as part of a nutritional intervention regimen to the current standard of care, namely, intermittent Androgen Deprivation Therapy (iADT), for patients with castration sensitive biochemical progressive prostate cancer. The main objectives are: * Assess the feasibility of the study population and enrollment. * Evaluate time to PSA relapse with nutritional intervention on iADT. Participants who are receiving iADT will be dispensed Metformin and turmeric and complete a pill diary. Participants will also have blood and stool samples collected and complete quality of life questionnaires. The long-term goal is to further assess the efficacy and safety of this nutritional regimen and the roles of metabolic syndrome, microenvironment/microbiome, and genomic vs epigenomic profiles in the care of these patients through a clinical trial.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you will need to stop taking your current vitamin and mineral supplements and use only those provided by the study. Herbal supplements can still be used.

What data supports the effectiveness of the drug Metformin for prostate cancer?

Research suggests that Metformin, a drug commonly used for diabetes, may help improve outcomes in prostate cancer patients by lowering the risk of cancer recurrence and stabilizing PSA levels, which are markers of prostate cancer activity. ^{1 2 3 4 5}

Is the combination of turmeric and metformin safe for humans?

The safety of dietary curcumin (from turmeric) in humans is well-documented, although it has low bioavailability (how well it is absorbed and used by the body). Metformin, commonly used for diabetes, has been studied for its potential effects on prostate cancer, but specific safety data for the combination of turmeric and metformin in humans is not provided in the available research. ^{6 7 8 9 10}

How does the drug Turmeric + Metformin differ from other prostate cancer treatments?

The combination of turmeric and metformin for prostate cancer is unique because turmeric contains curcumin, which can induce cancer cell death and inhibit growth, while metformin, a diabetes medication, has shown potential to enhance cancer treatment effects and reduce cancer-specific mortality. This combination targets cancer cells and the tumor environment, potentially keeping the cancer dormant and preventing its activation. ^{2 7 8 10 11}

Research Team

Shi-Ming Tu, MD

Principal Investigator

University of Arkansas

Eligibility Criteria

Men over 18 with prostate cancer who've had surgery or radiation, currently have rising PSA levels, and are on intermittent Androgen Deprivation Therapy (iADT). They must not have other active cancers or severe liver/renal disease, HIV, Hepatitis B/C, bone marrow issues, history of allergic reactions to turmeric/metformin, or risk factors for lactic acidosis.

Inclusion Criteria

Your serum PSA levels have increased consecutively over a period of at least one week.

I have had surgery or radiation for prostate cancer.

My PSA levels have doubled in less than 9 months.

Exclusion Criteria

Any other condition that, in the opinion of the investigator, might interfere with the safe conduct of the study.

I do not have active liver, kidney disease, HIV, Hepatitis B/C, or bone marrow issues.

I am allergic to turmeric, metformin, or similar substances.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intermittent Androgen Deprivation Therapy (iADT) along with metformin and turmeric as part of a nutritional intervention regimen

8 months

Regular visits for blood and stool sample collection and quality of life assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of PSA relapse and quality of life

19 months

Periodic assessments up to 27 months

Treatment Details

Interventions

• Metformin and Turmeric

Trial Overview The trial is testing the addition of metformin and turmeric to standard iADT in men with castration sensitive prostate cancer showing biochemical progression. It aims to see if this nutritional intervention affects the time until PSA levels rise again.

Participant Groups

Group I: Metformin + Turmeric Experimental Treatment 2 Interventions

Each subject will begin using metformin and turmeric within 7 days of consent. Subjects will start with metformin 500 mg by mouth (po) two times daily (bid) with meals for 14 days. Metformin titration will then increase to 850 milligram (mg) po bid for 14 days before increasing titration to a desired dosage of 1,000 mg po bid. For those subjects currently taking Metformin, they will continue current dose (if 1,000 mg po bid) or titrate dose as just described until maximum dose is achieved. After two weeks of metformin titration, each subject will start with 1,500 mg turmeric po daily with meals. Dose can be temporarily reduced to 1,000 mg po daily for those who report GI discomfort. If GI discomfort has resolved within one month of the dose reduction, subjects will resume 1,500 mg po daily. If GI discomfort has not resolved the participant may be insturcted to stop taking the study treatment and be removed from the study.

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Findings from Research

Metformin use in prostate cancer patients showed a marginal association with reduced risk of biochemical recurrence, with a pooled hazard ratio of 0.82, suggesting it may help prevent the return of cancer after treatment.

However, metformin did not significantly impact the risk of metastases, all-cause mortality, or prostate cancer-specific mortality, indicating that more rigorous randomized trials are needed to confirm its efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. Raval, AD., Thakker, D., Vyas, A., et al.[2018]

In a study comparing prostate cancer patients with type 2 diabetes who were on metformin to matched controls, those on metformin experienced significantly lower rates of death (10% vs 23%), recurrences (8% vs 15%), and metastases (0% vs 5%).

The metformin group also showed a trend towards lower prostate-specific antigen (PSA) levels, suggesting better disease control, which warrants further investigation in prospective studies for long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Patients With Type 2 Diabetes Mellitus. Chong, RW., Vasudevan, V., Zuber, J., et al.[2022]

In a study of 1314 men with prostate cancer who underwent surgery, those using antidiabetic drugs, including metformin, were found to have a higher prevalence of high-grade tumors, indicating a potential link between diabetes medication and tumor aggressiveness.

Despite the association with higher-grade tumors, the use of antidiabetic drugs did not significantly affect the risk of biochemical recurrence or disease-specific survival in the short term, suggesting that while these drugs may influence tumor characteristics, they do not necessarily worsen outcomes after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor features and survival after radical prostatectomy among antidiabetic drug users. Joentausta, RM., Kujala, PM., Visakorpi, T., et al.[2022]

Metformin is a safe and well-tolerated medication that can be used alongside standard treatments for prostate cancer, potentially reducing side effects from castration.

The STAMPEDE trial, starting in summer 2016, will evaluate the effectiveness of metformin as a repurposed treatment for men with high-risk prostate cancer, aiming to confirm its additional anticancer benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. Gillessen, S., Gilson, C., James, N., et al.[2021]

In a phase 2 trial involving 44 men with castration-resistant prostate cancer, treatment with metformin resulted in 36% of patients being progression-free at 12 weeks, indicating potential disease stabilization.

Metformin was found to be safe for nondiabetic patients and led to a prolongation of prostate-specific antigen (PSA) doubling time in over half of the participants, suggesting it may have beneficial effects on prostate cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). Rothermundt, C., Hayoz, S., Templeton, AJ., et al.[2015]

In a study of 1,034 patients undergoing prostate biopsies, metformin use among diabetic patients did not show any significant impact on the incidence of prostate cancer compared to nondiabetic patients.

Factors such as age, PSA velocity, and body mass index were more predictive of aggressive prostate cancer characteristics than diabetes or metformin use, indicating that metformin does not influence prostate cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of Disease After Transperineal Template-guided Mapping Biopsy. Merrick, GS., Bennett, A., Couture, T., et al.[2017]

Curcumin, a compound found in turmeric, has been identified as a potent inducer of apoptosis (programmed cell death) in both androgen-dependent and hormone-refractory prostate cancer cells, suggesting its potential as a nontoxic treatment option.

The mechanism of action involves curcumin down-regulating proteins that suppress apoptosis and the androgen receptor, which may help prevent the progression of prostate cancer to a more advanced, treatment-resistant stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. Dorai, T., Gehani, N., Katz, A.[2019]

The combination of curcumin and dutasteride significantly suppressed the proliferation of LNCaP prostate cancer cells and induced apoptosis, suggesting a potential therapeutic strategy for prostate cancer treatment.

This combination treatment also reduced levels of testosterone and dihydrotestosterone in the cancer cells, indicating it may effectively interfere with androgen activity within tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Curcumin Combined With the 5-alpha Reductase Inhibitor Dutasteride on LNCaP Prostate Cancer Cells. Nakayama, A., Ide, H., Lu, Y., et al.[2021]

Curcumin shows promise as a treatment for castration-resistant prostate cancer due to its ability to target multiple pathways, although its low bioavailability limits its effectiveness as a drug.

Research has led to the development of curcumin-based compounds that enhance its anticancer potential and improve pharmacokinetics, making them more suitable for clinical use in prostate cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin-based anti-prostate cancer agents. Chen, QH.[2019]

Metformin, derived from a natural ingredient, has shown potential to enhance the effectiveness of cancer treatments and reduce mortality in prostate cancer patients.

A combination treatment with metformin and Zyflamend, an herbal extract blend, may help keep cancer dormant by targeting cancer stem cells and the tumor microenvironment, as observed in the clinical responses of four patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series. Bilen, MA., Lin, SH., Tang, DG., et al.[2020]

Demethoxycurcumin (DMC) was found to be the most effective curcuminoid in killing prostate cancer PC3 cells, showing significant cytotoxic effects.

DMC works by activating AMPK, which reduces the activity of lipogenic enzymes and promotes apoptosis through the down-regulation of heat shock protein 70 (HSP70) and sustained activation of the epidermal growth factor receptor (EGFR).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. Hung, CM., Su, YH., Lin, HY., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. [2018]

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

Metformin Has a Positive Therapeutic Effect on Prostate Cancer in Patients With Type 2 Diabetes Mellitus. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Tumor features and survival after radical prostatectomy among antidiabetic drug users. [2022]

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

Repurposing Metformin as Therapy for Prostate Cancer within the STAMPEDE Trial Platform. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Metformin in chemotherapy-naive castration-resistant prostate cancer: a multicenter phase 2 trial (SAKK 08/09). [2015]

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

Metformin Does Not Predict for Prostate Cancer Diagnosis, Grade, or Volume of Disease After Transperineal Template-guided Mapping Biopsy. [2017]

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

Therapeutic potential of curcumin in human prostate cancer-I. curcumin induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cells. [2019]

8. Greece pubmed.ncbi.nlm.nih.gov

Effects of Curcumin Combined With the 5-alpha Reductase Inhibitor Dutasteride on LNCaP Prostate Cancer Cells. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Curcumin-based anti-prostate cancer agents. [2019]

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

Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series. [2020]

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

Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. [2019]