Metformin and Remote Monitoring for Brain Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Metformin, Resveratrol, CoQ10, others

Disqualifiers: Pregnancy, Nursing, Imprisonment, others

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

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

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

Compensation: Varies

Number of Visits: 30

Duration: 12 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two key aspects for people with brain tumors who need or have had radiation treatment: the potential benefits of the diabetes drug metformin and the feasibility of managing care remotely. Researchers aim to determine if metformin can reduce cognitive issues, such as difficulties with thinking and memory, following radiation. Participants will either receive metformin or continue their usual care, with both groups using wearable devices to monitor health and complete cognitive tests. Individuals with a brain tumor requiring cranial radiation, who can meet the study's requirements, might be suitable candidates for this trial. As a Phase 2 trial, this research measures how well metformin works in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires you to stop taking resveratrol, CoQ10, coconut oil, and curcumin supplements before joining and remain off them during the study. If you are currently taking metformin, you must be able to safely stop if assigned to the control group.

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

Research has shown that metformin, a drug commonly used for type 2 diabetes, has been studied for its safety in cancer treatments. In a small trial with 24 participants who received brain radiation, metformin proved to be safe and tolerable, suggesting it might be well-tolerated for others in similar situations. Additionally, studies indicate that metformin may offer benefits against brain tumors such as glioma, a type of brain cancer. While more research continues, these early findings provide reassurance about using metformin in new ways, such as in the trial under consideration. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using metformin for brain cancer because it offers a fresh approach compared to traditional treatments like surgery, radiation, and chemotherapy. Metformin, commonly used for diabetes, may affect cancer cell metabolism, potentially slowing tumor growth. Additionally, the integration of remote health monitoring with wearable devices allows for real-time tracking of patient health and cognitive function, making the treatment more personalized and proactive. This combination of a novel application of a well-known drug with cutting-edge technology could bring new hope for managing brain cancer.

What evidence suggests that metformin and remote monitoring could be effective for brain cancer?

Research shows that metformin, a drug often used to treat type 2 diabetes, might help slow memory and thinking problems after brain radiation. In this trial, participants in Group A will receive metformin. Studies have found that metformin can affect changes in brain tumors, such as glioblastoma, and may help stop their growth. Some research also suggests that metformin works well with other cancer treatments to improve outcomes. While more information is needed to confirm these benefits, early findings offer hope for brain cancer patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Ugur T. Sener, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients who have had cranial radiation therapy due to brain cancer or tumors. It's designed to see if care can be managed remotely using a web platform and wearable devices, and whether metformin helps prevent cognitive decline post-radiation.

Inclusion Criteria

Ability to complete cognitive assessments and questionnaires by themselves or with assistance

I am mostly active and can care for myself, with a KPS score of 70 or more.

Expected survival ≥ 6 months in the opinion of treatment team

Exclusion Criteria

I do not have any health issues that would make it unsafe for me to join the study.

I am not pregnant, nursing, imprisoned, or unable to understand my condition.

Known hypersensitivity or allergy to metformin

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or standard of care treatment for 12 months, with wearable device monitoring and neurocognitive tests

12 months

Monthly remote assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Follow-up at 30 days, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests remote patient care via the Mayo Test Drive platform and monitors physical activity with wearable devices. It also examines if metformin reduces cognitive issues after skull radiation compared to those not taking it.

How Is the Trial Designed?

Group I: Group A (metformin) Experimental Treatment 4 Interventions

Patients receive metformin PO BID for 12 months. Treatment repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also wear a wearable device to monitor health and undergo neurocognitive test throughout the study.

Group II: Group B (usual care) Active Control 4 Interventions

Patients receive SOC treatment for 12 months. Patients also wear a wearable device to monitor health and undergo neurocognitive test throughout the study.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Metformin (MET) significantly reduces the viability and proliferation of glioblastoma endothelial cells, promoting apoptosis through increased activity of caspases 3/7, indicating its potential as a therapeutic agent against this aggressive brain cancer.

MET also decreases angiogenesis and invasiveness in glioblastoma cells by altering sphingolipid metabolism, suggesting it could be safely repurposed as an add-on therapy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Metformin as Add-On Therapy against Glioblastoma: An Old Medicine for Novel Oncology Therapeutics. Guarnaccia, L., Navone, SE., Masseroli, MM., et al.[2022]

Metformin, an anti-diabetic drug, was found to decrease cell survival in glioblastoma multiforme (GBM) cells and reduce the expression of certain microRNAs associated with tumor aggressiveness, suggesting its potential as a therapeutic agent against GBM.

The study showed that metformin increased the expression of proteins involved in exosome biogenesis and secretion, indicating that it may enhance the release of exosomes from GBM cells, which could influence tumor behavior and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin Increases Exosome Biogenesis and Secretion in U87 MG Human Glioblastoma Cells: A Possible Mechanism of Therapeutic Resistance. Soraya, H., Sani, NA., Jabbari, N., et al.[2021]

In a pooled analysis of 1,731 glioblastoma patients from three clinical trials, metformin use was not significantly associated with improved overall survival (OS) or progression-free survival (PFS) during or after treatment with radiochemotherapy.

While there was a nonsignificant trend suggesting potential benefits of metformin monotherapy at baseline, this effect was not observed during concurrent treatment with temozolomide and radiotherapy, indicating that metformin does not prolong survival in newly diagnosed glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of metformin and outcome of patients with newly diagnosed glioblastoma: Pooled analysis. Seliger, C., Genbrugge, E., Gorlia, T., et al.[2020]

In a study of 276 glioblastoma patients, persistent high blood sugar levels and corticosteroid therapy were linked to lower survival rates, highlighting their negative impact on patient outcomes.

Diabetic patients treated with metformin showed longer progression-free survival, suggesting that metformin may have a beneficial effect in managing glioblastoma, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin influences progression in diabetic glioblastoma patients. Adeberg, S., Bernhardt, D., Ben Harrabi, S., et al.[2022]

Current evidence suggests that metformin, an oral antidiabetic drug, may have beneficial effects when used alongside chemotherapy for brain cancer treatment, particularly gliomas.

Further research is necessary to fully understand the relationship between diabetes, metabolism, and cancer, as brain tumors have a high mortality rate despite existing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidiabetic pharmacology: a link between metabolic syndrome and neuro-oncology? Aldea, M., Tomuleasa, C., Petrushev, B., et al.[2017]

In a phase II clinical trial involving 81 patients with recurrent or refractory glioblastoma, the combination of metformin and low-dose temozolomide was well tolerated but did not show a significant clinical benefit in terms of progression-free survival or overall survival compared to the control group receiving placebo and temozolomide.

The median overall survival was 17.22 months for the metformin group versus 7.69 months for the control group, but this difference was not statistically significant, indicating that metformin may not improve outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of metformin plus low-dose temozolomide in patients with recurrent or refractory glioblastoma: a randomized, prospective, multicenter, double-blind, controlled, phase 2 trial (KNOG-1501 study). Yoon, WS., Chang, JH., Kim, JH., et al.[2023]

In a phase I/II study involving patients with newly diagnosed glioblastoma, metformin (MF) was well tolerated at doses up to 2250 mg/day when combined with maintenance temozolomide (TMZ), with no dose-limiting toxicities observed.

The study showed that while some patients experienced tumor progression, five out of eight patients remained stable, suggesting potential benefits of MF in managing glioblastoma after standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin with Temozolomide for Newly Diagnosed Glioblastoma: Results of Phase I Study and a Brief Review of Relevant Studies. Ohno, M., Kitanaka, C., Miyakita, Y., et al.[2022]

In a study of 241 glioblastoma patients, metformin use was linked to longer overall survival, particularly in those with tumors that had a methylated MGMT promoter, showing a survival time of 484 days compared to 394 days for non-users.

Cox regression analysis indicated that metformin significantly reduced the risk of death at 2 years for patients with methylated MGMT promoters, suggesting it may be an effective adjunct treatment for this specific group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin use is associated with longer survival in glioblastoma patients with MGMT gene silencing. Mohammad, AH., Jatana, S., Ruiz-Barerra, MA., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1936523325000543

Metformin and glioma: Targeting metabolic dysregulation ... Altogether, these data have shown a promising role of metformin as a potential anticancer treatment in glioblastoma. In addition, researchers have evaluated ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9454846/

Metformin with Temozolomide for Newly Diagnosed ... We showed that the antidiabetic drug metformin (MF) can induce the differentiation of stem-like glioma-initiating cells and suppress tumor ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2051

Phase I/II study of maintenance therapy with metformin and ... Our phase I findings indicated that MF at doses of up to 2,250 mg/day combined with maintenance TMZ was well tolerated (Cancers, 2022). Here, we ...

4. mdpi.com mdpi.com/1422-0067/25/11/5694

Advances in Anti-Cancer Drug Development: Metformin as ... Clinical trials focusing on the combined use of metformin and temozolomide have highlighted significant improvements in treatment outcomes, which are promising ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7016983/

Metformin as Potential Therapy for High-Grade Glioma - PMC Metformin has a number of physicochemical characteristics that would promote its use in the treatment of brain tumors if its effectiveness were confirmed.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10244311/

Efficacy and safety of metformin plus low-dose temozolomide ... Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical ...

7. ispor.org ispor.org/heor-resources/presentations-database/presentation-cti/ispor-2025/poster-session-5/metformin-exposure-and-survival-in-glioblastoma-a-large-population-study

Metformin Exposure and Survival in Glioblastoma RESULTS: Among 16,069 patients diagnosed with GBM, 2,589 (16.1%) were exposed to metformin after diagnosis, and 8,964 (55.8%) died within 6 months of diagnosis.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05230758

Study Details | NCT05230758 | Effect of Metformin on ... In a pilot trial with 24 participants, we found that metformin was safe and tolerable for use in children/adolescents treated with cranial radiation for a ...