Time-Restricted Diet for Brain Metastases

Overseen By Nicole Simone, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Thomas Jefferson University

Disqualifiers: Intractable seizures, Glioma, others

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

Compensation: Varies

Number of Visits: 4

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial tests the effectiveness of an interactive time-restricted diet intervention (txt4fasting) in reducing neurocognitive decline and improving survival outcomes after stereotactic radiosurgery in patients with breast or lung cancer that has spread to the brain (brain metastases). Lung cancer and breast cancer are the two most frequent causes of brain metastases. The diagnosis of brain metastases is associated with poorer survival and tumor-induced and treatment-related side effects. Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. Patients who receive stereotactic radiosurgery for brain metastases may experience less neurocognitive side effects than with other types of brain radiation, but may still be at risk for their brain metastases growing, spreading, or getting worse. Patients with obesity and diabetes have been shown to have worse survival and increased radiation-related side effects. Evidence demonstrates that simply changing meal timing can have a positive impact on multiple health outcomes. Time-restricted eating, or prolonged nighttime fasting, has been proven to have positive effects on heart disease risk reduction, weight control management and chemotherapy side effect reduction. Txt4fasting may be effective in decreasing neurocognitive decline and improving survival outcomes in patients undergoing stereotactic radiosurgery for brain metastases from breast or lung cancer.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. In fact, chemotherapy, hormone, and immune therapy are allowed to be taken at the same time as the trial.

What data supports the effectiveness of the treatment Interactive Time-Restricted Diet Intervention (txt4fasting), Time-Restricted Eating, Prolonged Nighttime Fasting for brain metastases?

Research shows that time-restricted feeding can reduce cancer spread and improve survival in animal models, suggesting it might help manage cancer in humans. For example, studies found that time-restricted feeding reduced tumor growth and spread in mice with breast cancer and improved survival in rats with tumors. ^{1 2 3 4 5}

Is time-restricted feeding safe for humans?

Time-restricted feeding (TRF) has been studied in humans and appears to be safe, showing mild weight loss and improvements in some heart and metabolism-related health factors without the need for calorie counting. ^{1 2 4 6 7}

How does the time-restricted diet treatment differ from other treatments for brain metastases?

The time-restricted diet treatment is unique because it focuses on controlling the timing of food intake rather than the type or amount of food, aiming to improve health by aligning eating patterns with natural body rhythms. This approach is different from traditional treatments that may focus on medication or surgery, and it has shown potential in reducing tumor growth and improving survival in animal studies by promoting a healthier metabolic environment. ^{1 2 5 8 9}

Eligibility Criteria

This trial is for breast or lung cancer patients with brain metastases, who will undergo stereotactic radiosurgery. It's designed to see if a special diet plan that changes when you eat can help reduce mental decline and improve survival rates.

Inclusion Criteria

Willing and able to comply with the protocol for the duration of the study

Body mass index (BMI) ≥ 25 kg/m^2

Able to speak, read and write English

Exclusion Criteria

Inability to tolerate a normal diet (may include an active malabsorption syndrome at the time of consent [i.e. Crohn's disease, major bowel resection leading to permanent malabsorption])

Not a SRS candidate as determined by the treating physician

I have not had brain surgery in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants follow a time-restricted diet and receive interactive messages for 30 days, with counseling calls and food intake recording

4 weeks

Counseling calls twice weekly in weeks 1 and 2, then once weekly in weeks 3 and 4

Stereotactic Radiosurgery (SRS)

Participants undergo stereotactic radiosurgery and have blood samples and brain MRI collected

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at 3 and 6 months

6 months

Follow-up visits at 3 and 6 months

Treatment Details

Interventions

• Interactive Time-Restricted Diet Intervention (txt4fasting)

Trial Overview The study tests an interactive diet intervention called txt4fasting, which involves time-restricted eating to potentially benefit the brain after radiation therapy. Patients will also receive dietary counseling and be monitored through various assessments and imaging.

Participant Groups

Group I: Arm I (txt4fasting) Experimental Treatment 10 Interventions

Patients follow a time-restricted diet, receive interactive positive reinforcement messages, and record food intake using the txt4fasting platform daily for 30 days. Patients receive counseling calls twice weekly in weeks 1 and 2 then once weekly in weeks 3 and 4. Patients then undergo SRS on study. Patients also undergo blood sample collection and brain MRI throughout study.

Group II: Arm II (attention control) Active Control 8 Interventions

Patients receive text messages about healthy eating habits and food suggestions twice daily and record food intake using txt4fasting program for 30 days. Patients then undergo SRS on study. Patients also undergo blood sample collection and brain MRI throughout study.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

Findings from Research

Time-restricted feeding during the dark phase significantly reduced the risk of mammary tumor development in mice fed a high-fat diet (HFD), suggesting a protective effect against tumorigenesis.

The study found that while the HFD group had increased body fat and tumor progression, the restricted feeding group maintained body fat levels similar to a standard diet, indicating that timing of food intake may influence metabolic health and cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. Sundaram, S., Yan, L.[2019]

Time-restricted feeding (TRF) significantly reduces the risk of obesity-related metastasis in a mouse model of lung cancer, as shown by lower numbers and sizes of lung metastases compared to those on a high-fat diet (HFD).

TRF also effectively prevents increases in harmful substances like glucose, insulin, and proinflammatory cytokines that are typically elevated by a high-fat diet, suggesting a protective mechanism against cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted Feeding Attenuates High-fat Diet-enhanced Spontaneous Metastasis of Lewis Lung Carcinoma in Mice. Yan, L., Sundaram, S., Mehus, AA., et al.[2019]

A pilot study involving 40 women with a history of early-stage breast cancer showed that prolonged overnight fasting (POF) for 13 hours was feasible, with 95% of participants successfully fasting for at least 70% of the study nights.

Participants experienced significant improvements in anxiety, BMI, depression, and fatigue after 12 weeks of fasting, suggesting that POF may be a beneficial nonpharmacological intervention for improving certain health outcomes in breast cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study to assess prolonged overnight fasting in breast cancer survivors (longfast). O'Donnell, E., Shapiro, Y., Comander, A., et al.[2022]

Time-restricted feeding (TRF) effectively reduces mammary tumor growth and metastasis in mouse models of obesity-driven postmenopausal breast cancer without requiring calorie restriction or weight loss.

TRF improves insulin sensitivity and normalizes circadian gene expression in tumors, indicating that its cancer-fighting effects may be linked to its ability to lower hyperinsulinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models. Das, M., Ellies, LG., Kumar, D., et al.[2023]

Short-term dietary restriction, involving alternate day feeding and fasting, significantly improved survival rates in tumor-bearing Fisher rats, with 66.7% surviving 9 days post-tumor inoculation compared to only 20.8% in the control group.

The study suggests that mild dietary restrictions could be beneficial in enhancing survival and potentially inhibiting cancer growth, indicating a need for further clinical trials in human cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Siegel, I., Liu, TL., Nepomuceno, N., et al.[2019]

In a study involving adults with obesity, both 4-hour and 6-hour time-restricted feeding (TRF) regimens led to comparable weight loss of about 3% over 8 weeks, along with improvements in insulin resistance and oxidative stress.

Participants in the TRF groups reduced their daily energy intake by approximately 550 kcal without needing to count calories, suggesting that TRF can be an effective and manageable approach for weight loss and improving cardiometabolic health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 4- and 6-h Time-Restricted Feeding on Weight and Cardiometabolic Health: A Randomized Controlled Trial in Adults with Obesity. Cienfuegos, S., Gabel, K., Kalam, F., et al.[2022]

Time-restricted feeding (TRF) significantly reduced the expression of genes related to lipid metabolism in mammary tumors, suggesting a potential mechanism for its protective effects against tumor development.

Despite TRF not altering the overall metabolic profile of the tumors, its protective effects may be due to changes in the host's biological pathways rather than direct effects on tumor metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. Yan, L., Sundaram, S., Rust, BM., et al.[2020]

A moderate dietary restriction of 30-40% significantly reduced the growth of malignant brain tumors in mice by nearly 80%, indicating its potential as a therapeutic strategy.

The study found that dietary restriction led to lower tumor blood vessel density and increased tumor cell death, suggesting it may shift the tumor environment to inhibit growth and promote apoptosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Mukherjee, P., El-Abbadi, MM., Kasperzyk, JL., et al.[2022]

Chronic dietary restriction, specifically a 50% reduction in diet for one week before and three weeks after tumor inoculation, significantly reduces lung metastasis in rats, indicating a potential strategy for inhibiting tumor growth.

The study found that preexposure to dietary restriction is crucial for reducing tumor colonization, and this effect may be linked to increased activity of natural killer cells shortly after tumor inoculation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic dietary restriction influences tumor metastasis in the rat: parametric considerations. Hodgson, DM., Chiappelli, F., Morrow, NS., et al.[2007]

References

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

Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

Time-restricted Feeding Attenuates High-fat Diet-enhanced Spontaneous Metastasis of Lewis Lung Carcinoma in Mice. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Pilot study to assess prolonged overnight fasting in breast cancer survivors (longfast). [2022]

4. England pubmed.ncbi.nlm.nih.gov

Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models. [2023]

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

Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. [2019]

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

Effects of 4- and 6-h Time-Restricted Feeding on Weight and Cardiometabolic Health: A Randomized Controlled Trial in Adults with Obesity. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. [2022]

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

Chronic dietary restriction influences tumor metastasis in the rat: parametric considerations. [2007]