Ketogenic Diet for Brain Cancer

(Ketones Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Michigan State University

Must not be taking: Glucocorticosteroids

Disqualifiers: Diabetes, Cholecystectomy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether an energy-restricted ketogenic diet can help treat primary brain cancer by shrinking the cancer or stopping its growth. Similar to a diet used for children with seizures, it involves eating foods that lower blood sugar while raising ketones, which are energy molecules produced when the body burns fat. The study also aims to identify any side effects this diet might have for brain cancer patients. Individuals with glioblastoma multiforme, a type of brain cancer, who have measurable disease after standard treatments might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to explore a potentially groundbreaking dietary approach to brain cancer treatment.

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 prior data suggests that this diet is safe for treating brain cancer?

Research shows that the energy-restricted ketogenic diet (ERKD) is safe for people with brain tumors. Previous studies have found that patients can easily follow this diet without major side effects. For instance, one study found that patients adhered to the diet without significant issues. Additionally, the diet has been used successfully in children with seizures, with only minor side effects reported. This suggests that the diet is generally safe for people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for glioblastoma multiforme, like radiation and the chemotherapy drug temozolomide, focus on attacking cancer cells directly. But the ketogenic diet works differently. Researchers are excited about this treatment because it alters the body's metabolism to produce ketones instead of glucose for energy, which may make it harder for cancer cells to thrive. This dietary approach is non-invasive and is tailored to each patient's needs based on their blood ketone levels, potentially offering a new supportive strategy alongside traditional treatments.

What evidence suggests that the energy restricted ketogenic diet might be an effective treatment for primary brain cancer?

This trial will evaluate adding a ketogenic diet to the standard initial treatment for glioblastoma multiforme. Studies have suggested that a ketogenic diet might extend the lives of people with brain tumors. In one study, patients who followed this diet had a 66.7% survival rate compared to those who did not. Another report indicated that the diet is safe and can be used alongside standard brain cancer treatments. By maintaining low blood sugar levels and increasing ketones, this diet might help slow or stop cancer growth. While more research is needed, early findings are promising for those with brain cancers like glioblastoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Kenneth Schwartz, MD

Principal Investigator

Michigan State University

Are You a Good Fit for This Trial?

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

Inability to adhere to or tolerate dietary protocol

Pregnancy

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

The Role of the Ketogenic Diet in Managing Glioblastoma in ...

According to the findings of our study, patients with brain tumors who stick to a ketogenic diet are more likely to experience improved survival rates.

2.

ascopubs.org

ascopubs.org/doi/10.1200/jco.2013.31.15_suppl.e13047

Treatment of advanced glioma with an energy restricted ...

Background: We initiated a pilot study to evaluate an energy restricted ketogenic diet (ERKD) as treatment for patients with glioblastoma ...

3.

frontiersin.org

frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1489812/full

Successful application of dietary ketogenic metabolic ...

Consequently, the survival rate among these patients is 4 out of 6, or 66.7%. Of the 12 patients who did not adhere to the diet, only one reached 36 months of ...

4.

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 ...

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0007455125003327

Prospects of the therapeutic approaches of ketogenic diet ...

Nearly almost of the studies found that there was a potential role of KD in the prognosis of cancer treatment. The current review suggests that cancer patients ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01535911?term=ketogenic%20diet&cond=Glioblastoma%20Multiforme&viewType=Table&rank=7

Pilot Study of a Metabolic Nutritional Therapy for the ...

A nutritionally adequate but energy restricted, ketogenic diet (ERKD) to deprive brain tumors of energy and resulting in death of glioma cells is promising.

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4371612/

Treatment of glioma patients with ketogenic diets: report of two ...

We conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in ...