Ketogenic Diet + Metformin for Glioblastoma

Recruiting at 1 trial location

Overseen By Devonie Manzano, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Metformin

Must not be taking: Insulin, Oral hypoglycemics

Disqualifiers: Diabetes, Other malignancy, Alcoholism, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketogenic diet (high fat, low carb) combined with metformin, a diabetes drug, can help treat high-grade brain tumors like glioblastoma by lowering blood sugar, potentially slowing tumor growth. Participants will prepare their own meals with a nutritionist's guidance and remain on the diet as long as it proves effective and does not cause major side effects. This trial may suit individuals with a confirmed diagnosis of high-grade brain tumors who are not currently taking diabetes medication or involved in other experimental treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to early evidence of its effectiveness.

Will I have to stop taking my current medications?

If you are taking insulin or other oral diabetes medications, you will need to stop them at least 6 weeks before joining the trial. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that the ketogenic diet and metformin are likely to be safe for humans?

Research has shown that both the ketogenic diet and metformin have safety data worth considering. A ketogenic diet, high in fat and low in carbohydrates, is generally safe for people with glioblastoma, a type of brain tumor. This diet may help extend life and reduce symptoms like fatigue and sleep disturbances.

Metformin, a common diabetes medication, is also under study for its potential to treat glioma. Research indicates it is generally well-tolerated. Although some studies did not show clear survival benefits, metformin has been safely used in patients and may be effective when combined with other treatments.

These findings suggest that using a ketogenic diet and metformin together is likely safe, but further studies are needed to confirm their effects on people with brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for glioblastoma?

Researchers are excited about the combination of a ketogenic diet and metformin for glioblastoma because it offers a novel approach compared to traditional treatments like surgery, radiation, and chemotherapy. Unlike these standard options, which directly target tumor cells, the ketogenic diet aims to starve cancer cells by reducing glucose availability, while metformin may enhance this effect by influencing cellular metabolism. This dual strategy targets the energy supply and metabolic pathways of cancer cells, potentially slowing their growth and making them more vulnerable, which is a promising avenue for improving patient outcomes in a condition that's notoriously difficult to treat.

What evidence suggests that the ketogenic diet and metformin might be effective for glioblastoma?

This trial will evaluate the effects of a ketogenic diet and metformin on glioblastoma. Studies have shown that the ketogenic diet can help shrink tumors in patients with glioblastoma, a type of brain cancer. Specifically, one study found that tumors were much smaller after 90 days on the diet compared to the start of the study. Research also suggests that a ketogenic diet might improve cancer outcomes more effectively than other diets. Metformin, a drug often used for type 2 diabetes, lowers blood sugar levels, which is important because sugar can help tumors grow. Together, the ketogenic diet and metformin reduce the sugar available to the tumor, potentially slowing its growth. ^{1 2 3 5 6}

Who Is on the Research Team?

Howard Fine, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade gliomas who haven't had bevacizumab therapy. They should not have diabetes requiring medication, no recent malignancy treatments (except certain skin cancers), and no severe illnesses that could affect study participation. Participants must be able to prepare meals and follow a ketogenic diet with metformin, without experiencing unacceptable side effects.

Inclusion Criteria

I don't need to be tumor-free after surgery to join the study.

Life expectancy of greater than 12 weeks.

- Total bilirubin <2.0 X institutional upper limit of normal (unless known to have Gilbert's Disease)

Exclusion Criteria

I do not have any serious illnesses that are not under control.

I haven't taken insulin or diabetes pills for at least 6 weeks.

I have not been treated for cancer (except skin cancer or cervical pre-cancer) in the last year and don't expect to need treatment in the next year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a ketogenic diet and take metformin to evaluate tolerability and metabolic effects

8 months

Regular visits with a nutritionist for meal planning and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Metformin

Trial Overview The trial tests the combination of a ketogenic diet and metformin on patients with high-grade gliomas. The goal is to see if this regimen can lower blood glucose levels which may contribute to slowing tumor growth. Patients will work with a nutritionist to manage their diet while taking metformin.

How Is the Trial Designed?

Group I: Ketogenic Diet Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

The therapeutic ketogenic diet (KD) enhances the immune response against glioblastoma in mice, leading to increased activity of tumor-reactive CD8+ T cells and natural killer (NK) cells, which may help in fighting the tumor.

Mice on the KD showed reduced expression of immune inhibitory receptors, suggesting that the diet alleviates immune suppression in the tumor microenvironment, potentially improving the effectiveness of other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet. Lussier, DM., Woolf, EC., Johnson, JL., et al.[2022]

The supplemented high-fat low-carbohydrate (sHFLC) diet effectively inhibits the growth of glioblastoma (GB) cells and reduces tumor stem cell expansion, showing promise as a less restrictive alternative to the ketogenic diet.

In preclinical models, the sHFLC diet not only slowed tumor progression but also improved survival rates, with its anticancer effects linked to the reduction of mTOR pathway activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Supplemented High-Fat Low-Carbohydrate Diet for the Treatment of Glioblastoma. Martuscello, RT., Vedam-Mai, V., McCarthy, DJ., et al.[2023]

The ERGO trial demonstrated that a ketogenic diet is feasible and safe for patients with recurrent glioblastoma, with 92% of evaluable patients achieving urinary ketosis and no serious adverse events reported.

While the ketogenic diet alone showed limited clinical activity, it appeared to enhance the effectiveness of bevacizumab, with a median progression-free survival of 20.1 weeks in patients combining the diet with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Rieger, J., Bähr, O., Maurer, GD., et al.[2023]

A retrospective study of 53 glioblastoma multiforme patients indicated that a ketogenic diet (KD) is safe and well tolerated during standard treatment, with no severe toxicities reported and only mild fatigue experienced.

Patients on a KD had significantly lower serum glucose levels (mean 84 mg/dl) compared to those on a standard diet (mean 122 mg/dl), suggesting that dietary carbohydrate restriction may positively influence treatment response and prognosis in GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. Champ, CE., Palmer, JD., Volek, JS., et al.[2022]

The pilot study of a 4:1 ketogenic diet (KD) using a total meal replacement program for glioblastoma (GBM) patients showed that the diet was well tolerated, with mild and transient treatment-emergent adverse events, and 62.5% of participants completed the 6-month treatment.

Survival times were promising, with a mean of 20 months for newly diagnosed patients and 12.8 months for recurrent GBM patients after starting the KD, suggesting potential benefits, although the small sample size limits definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. Klein, P., Tyrlikova, I., Zuccoli, G., et al.[2020]

A modified ketogenic diet (MKD) was well tolerated by glioma patients, with only minor side effects like constipation reported, and it was achievable within a standard healthcare service.

Out of 172 surveyed patients, 69% supported offering MKD as a treatment option, and 73% expressed willingness to try it for 3 months, indicating strong interest in future clinical trials to assess its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service. Martin-McGill, KJ., Marson, AG., Tudur Smith, C., et al.[2022]

A combined metabolic strategy of fasting and a ketogenic diet was found to be feasible and safe for 10 patients with glioblastoma multiforme (GBM), allowing them to maintain a therapeutic glucose ketone index (GKI) of 3.22 over a mean duration of 161 days.

The approach led to significant weight loss (average of 8.4 kg) and mild adverse effects like fatigue and irritability, without interfering with standard cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series. Phillips, MCL., Leyden, J., McManus, EJ., et al.[2022]

Preclinical studies indicate that ketogenic or caloric restricted diets (KCRDs) can reduce tumor growth in malignant gliomas, particularly when blood glucose levels are decreased, although improved survival was only observed in a minority of cases.

Preliminary clinical data suggest that KCRDs are safe and feasible for glioma patients, but there is not enough evidence yet to confirm their effectiveness in improving survival or quality of life, highlighting the need for further prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. Noorlag, L., De Vos, FY., Kok, A., et al.[2022]

A clinical trial involving 15 patients with glioblastoma multiforme (GBM) is exploring the addition of a ketogenic diet (KD) to standard treatments like surgery, radiation, and chemotherapy, aiming to improve survival rates beyond the current median of 8-15 months.

The study emphasizes the importance of standardized diet protocols and regular monitoring of patients' blood glucose and ketone levels to ensure compliance and optimize treatment effectiveness, particularly in patients with strong support systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned. Schwartz, KA., Noel, M., Nikolai, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11433106/

The Role of the Ketogenic Diet in Managing Glioblastoma in ... Imaging evaluation showed that tumor size was significantly reduced in the ketogenic diet group at 90 days compared with the baseline (p = 0.035) ...

2. cancerresearchuk.org cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-comparing-types-of-ketogenic-diet-in-people-with-glioblastoma-keating

A study comparing types of ketogenic diet in people with ... The study compared 2 types of ketogenic diets in people with a glioblastoma (GBM). Glioblastomas are a type of brain tumour. A ketogenic diet is high in fat ...

3. nature.com nature.com/articles/s41598-025-06675-6

A phase 1 safety and feasibility trial of a ketogenic diet plus ... This phase 1 trial demonstrates that KD is safe and feasible for GBM patients receiving SOC, may improve outcomes, and provides a foundation for an NCI-funded ...

4. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1535921/full

Impact of ketogenic diets on cancer patient outcomes Conclusion: The ketogenic diet was found to improve cancer patients' outcomes more effectively than non-ketogenic diets. Notably, C-reactive ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004220306453

Article Glioblastoma Utilizes Fatty Acids and Ketone Bodies ... However, the unrestricted ketogenic diet did not reduce tumor growth and for some models significantly reduced survival. Altogether, these data ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05183204?draw=2&rank=1

NCT05183204 | Paxalisib With a High Fat, Low Carb Diet ... The purpose of this study is to assess the safety of Paxalisib while maintaining a ketogenic diet (a high fat, low carbohydrate diet) and Metformin (a drug ...