Ketogenic Diet + Metformin for Glioblastoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Howard Fine, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is for men and women with aggressive brain tumors. It uses a high-fat, low-carb diet and a diabetes medication to lower blood sugar levels. The goal is to see if this approach can help slow down tumor growth. The high-fat, low-carb diet is being explored as an additional treatment for brain tumors, with some studies suggesting it may help control tumor growth and improve response to standard treatments.

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.

What data supports the effectiveness of the treatment Ketogenic Diet + Metformin for Glioblastoma?

Research suggests that a ketogenic diet, which is high in fat and low in carbohydrates, may help slow tumor growth and improve survival in glioblastoma patients. Studies in mice and early human trials indicate that this diet can enhance the immune response and is generally well-tolerated, though more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is the combination of a ketogenic diet and metformin safe for humans?

Research on the ketogenic diet for glioblastoma shows it is generally safe, with no serious side effects reported, though some patients may find it hard to tolerate. Metformin, commonly used for diabetes, is generally safe but can cause side effects like stomach upset and, rarely, a serious condition called lactic acidosis (buildup of lactic acid in the blood). ^{1 2 3 6 7}

How is the Ketogenic Diet + Metformin treatment for glioblastoma different from other treatments?

This treatment is unique because it combines a ketogenic diet, which lowers blood sugar and increases ketones, with Metformin, a drug that helps control blood sugar levels. This approach targets the cancer's metabolism, potentially slowing tumor growth by depriving it of glucose, which is different from traditional treatments that often focus on directly attacking the tumor cells. ^{1 3 6 8 9}

Research Team

Howard Fine, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Ketogenic Diet (Other)
• Metformin (Other)

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.

Participant Groups

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+

Dr. Robert Min

Weill Medical College of Cornell University

Chief Executive Officer since 2024

MD, MBA

Dr. Adam R. Stracher

Weill Medical College of Cornell University

Chief Medical Officer since 2024

MD

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

References

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

Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. [2020]

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

Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet. [2022]

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

Investigating the Ketogenic Diet As Treatment for Primary Aggressive Brain Cancer: Challenges and Lessons Learned. [2022]

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

The Modified Ketogenic Diet in Adults with Glioblastoma: An Evaluation of Feasibility and Deliverability within the National Health Service. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. [2023]

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

Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. [2022]

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

A Supplemented High-Fat Low-Carbohydrate Diet for the Treatment of Glioblastoma. [2023]

9. Egypt pubmed.ncbi.nlm.nih.gov

Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series. [2022]