Ketogenic Diet for Brain Cancer

(Ketones Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Michigan State University

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will look at the effects, good and/or bad, of treating primary brain cancers with diet therapy using an energy restricted ketogenic diet (ERKD) that uses food. An energy restricted ketogenic diet is a diet designed to keep blood sugars in the low range of normal while at the same time increasing the blood concentration of metabolic break down products called ketones. This diet is currently used to treat children with uncontrollable seizures. This diet is well tolerated by the children with minimal side effects reported after using the diet for years. * The main purpose of this study is to find out whether or not the energy restricted ketogenic diet will help patients with primary brain cancer by either decreasing the size of the cancer or by keeping the cancer from growing. * Another reason for doing this study is to learn about the side effects associated with the energy restricted ketogenic diet in patients with primary brain cancer.

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 cannot participate if you are using glucocorticosteroids or have diabetes treated with medication.

What data supports the effectiveness of the treatment Energy Restricted Ketogenic Diet for brain cancer?

Research suggests that the Energy Restricted Ketogenic Diet can be effective in slowing the growth of malignant brain cancer by reducing the availability of glucose, which tumor cells need to grow. Studies in mice and human case reports have shown that this diet can inhibit tumor growth and improve outcomes when combined with other treatments. ^{1 2 3 4 5}

Is the ketogenic diet safe for people with brain cancer?

The ketogenic diet has been studied for safety in people with brain cancer, and it is generally considered safe when used under medical supervision. Some studies have shown it to be a non-toxic option, but it can be challenging to follow due to its strict dietary requirements. ^{1 2 5 6 7}

How does the ketogenic diet treatment for brain cancer differ from other treatments?

The ketogenic diet for brain cancer is unique because it focuses on restricting energy intake through a high-fat, low-carbohydrate diet, which may alter the metabolism of cancer cells. This approach is different from traditional treatments like surgery, chemotherapy, and radiotherapy, which directly target tumor cells. ^{8 9 10 11 12}

Research Team

Kenneth Schwartz, MD

Principal Investigator

Michigan State University

Eligibility Criteria

This trial is for adults over 18 with a confirmed diagnosis of Glioblastoma (GBM) who have measurable disease after standard treatments. They should be able to perform daily activities with relative ease (ECOG ≤2), and have a life expectancy greater than 3 months. It's not suitable for those on diabetes medication, steroids, or with major organ failure, pregnant women, or anyone unable to follow the diet.

Inclusion Criteria

You are expected to live for more than 3 months.

I am over 18 and have a confirmed diagnosis of GBM.

I can take care of myself and perform daily activities.

Exclusion Criteria

I have cancer that needs treatment, but it's not a primary brain tumor.

Pregnancy

Inability to adhere to or tolerate dietary protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Intervention

Initial maximal tumor excision is performed

1 week

Treatment

Participants receive an energy restricted ketogenic diet (ERKD) along with radiation and chemotherapy

6 weeks

Inpatient admission or local outpatient visits

Extended Treatment

Continuation of ERKD as adjunctive therapy with standard chemotherapy

6 weeks

Follow-up

Participants are monitored for changes in tumor size and recurrence using MRI imaging

6 weeks

Treatment Details

Interventions

• Energy Restricted Ketogenic Diet

Trial Overview The study tests an energy restricted ketogenic diet (ERKD) that aims to maintain low blood sugar levels while increasing ketones in the body. This dietary approach has been used in children with seizures and may help shrink or stabilize primary brain tumors.

Participant Groups

Group I: Obsrvational study adding ketogenic diet to standard initial treatment of glioblastom multiforme Experimental Treatment 1 Intervention

Add ketogenic diet to standard tx of glioblastoma multiforme. After patients have recovered from surgical intervention patients are given a ketogenic diet along with standard of care, radiation and temozolomide treatments. The ketogenic diet is modified by dietitians based on twice daily measurements of blood ketone levels.

Who Is Running the Clinical Trial?

Michigan State University

Lead Sponsor

Trials

202

Recruited

687,000+

Sparrow Health System

Collaborator

Trials

8

Recruited

890+

Findings from Research

The restricted ketogenic diet (RKD) targets energy metabolism in malignant brain cancer by reducing glucose and glutamine availability, which are crucial for tumor growth, and has shown anti-cancer effects in mouse models.

Case reports indicate that the RKD can be an effective non-toxic treatment option for malignant gliomas in humans, potentially enhancing the efficacy of existing therapies that also target glucose and glutamine metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Seyfried, TN., Marsh, J., Shelton, LM., et al.[2017]

The ketogenic dietary intervention, known as the Glioma Atkins-Based Diet (GLAD), was feasible and safe for 25 patients with glioma, with 84% completing the 8-week study and significant metabolic changes observed, including increased ketone levels in the brain.

The diet led to meaningful systemic changes, such as decreased insulin and hemoglobin A1c levels, and increased ketone concentrations in both the tumor and healthy brain tissue, suggesting that ketonuria is a reliable indicator of metabolic activity in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. Schreck, KC., Hsu, FC., Berrington, A., et al.[2022]

A review of 13 studies involving 187 glioma patients indicates that ketogenic diets (KD) may inhibit glioma growth and help manage symptoms, but there is significant variability in how these diets are implemented.

The lack of standardization in ketogenic diet protocols for glioma patients complicates comparisons of their effectiveness, highlighting the need for a consensus on dietary definitions and methods to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View. Guo, A., Asztely, F., Smits, A., 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]

The restricted KetoCal diet significantly reduced tumor growth in mouse models of malignant brain cancer, decreasing growth by about 65% for CT-2A tumors and 35% for U87-MG tumors, while also improving overall health and survival compared to a standard high carbohydrate diet.

KetoCal's effectiveness is attributed to its ability to lower plasma glucose levels and increase ketone bodies, exploiting the tumors' reliance on glucose for energy, suggesting that this diet could be a safe and effective alternative therapy for managing malignant brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Zhou, W., Mukherjee, P., Kiebish, MA., et al.[2020]

The ERGO2 trial, involving 50 patients with recurrent brain tumors, found that a calorie-restricted ketogenic diet combined with intermittent fasting did not improve progression-free survival compared to a standard diet, despite achieving significant metabolic changes in those on the ketogenic diet.

Patients on the ketogenic diet successfully met their dietary goals, leading to notable decreases in leptin and insulin levels, while low glucose levels were identified as a potential marker for better prognosis, although quality of life and cognitive function remained unaffected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. Voss, M., Wenger, KJ., von Mettenheim, N., 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]

Malignant brain tumors remain difficult to treat, with long-term survival only improving from 6 to 15 months over the last 80 years, despite advancements in surgery, chemotherapy, and radiotherapy.

Immunotherapy, particularly using immune modulators like CTLA-4 and PD-1/PD-L1, is being actively researched in ongoing phase I and III trials, showing promise in targeting glioma antigens, but challenges remain in achieving complete responses and understanding the lack of adverse brain inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of EGFRvIII as the target for glioma vaccines. Lowenstein, PR., Castro, MG.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? [2017]

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

Feasibility and Biological Activity of a Ketogenic/Intermittent-Fasting Diet in Patients With Glioma. [2022]

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

Methodological Approaches to Ketogenic Dietary Treatments in Glioma Patients from a Nutritional Point of View. [2022]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial. [2022]

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

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

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Glioblastoma Multiforme and Adult Neurogenesis in the Ventricular-Subventricular Zone: A Review. [2017]

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The value of EGFRvIII as the target for glioma vaccines. [2021]

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