Time-Restricted Diet for Brain Metastases
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Thomas Jefferson University
Disqualifiers: Intractable seizures, Glioma, others
No Placebo Group
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.
12345Is 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.
12467How 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.
12589Eligibility 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
+6 more
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.
+2 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (txt4fasting)Experimental Treatment10 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 Control8 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, PA
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Who Is Running the Clinical Trial?
Thomas Jefferson UniversityLead Sponsor
References
Time-restricted feeding mitigates high-fat diet-enhanced mammary tumorigenesis in MMTV-PyMT mice. [2019]Erratic eating behavior disrupts the daily feeding and fasting pattern and leads to metabolic dysfunction and chronic diseases including cancer. In the present study, we tested the hypothesis that time-restricted feeding of a high-fat diet (HFD) to the dark phase does not enhance mammary tumorigenesis in MMTV-PyMT mice. Female mice were assigned to 3 groups and fed the standard AIN93G diet or an HFD with or without dark phase restricted feeding (12 hours). The duration of restricted feeding was 8 weeks. The HFD group had 24% more body fat mass than the AIN93G group; the body fat mass of the restricted group remained similar to that of the AIN93G group. Energy intake of the restricted group was similar to that of the HFD and AIN93G groups. The median mammary tumor latency was 5.8, 7.0, and 6.4 weeks for the AIN93G, HFD, and restricted groups, respectively. Mammary tumor progression was 241% higher in the HFD group than that in the AIN93G group; there was no significant difference in tumor progression between the restricted and AIN93G groups. Plasma concentrations of leptin, monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, angiopoietin-2, vascular endothelial growth factor, and hepatocyte growth factor were significantly higher in the HFD group than those in the control group; these measurements were similar between the restricted and control groups. In conclusion, feeding restricted to the dark phase mitigates the HFD-enhanced mammary tumorigenesis; this may be related to the lower body adiposity and associated inflammatory and angiogenic signals.
Time-restricted Feeding Attenuates High-fat Diet-enhanced Spontaneous Metastasis of Lewis Lung Carcinoma in Mice. [2019]Obesity is a risk factor for cancer. Disruption of the daily feeding and fasting rhythm can contribute to obesity. This study tested the hypothesis that time-restricted feeding (TRF) attenuates obesity-enhanced metastasis.
Pilot study to assess prolonged overnight fasting in breast cancer survivors (longfast). [2022]Retrospective analysis of nightly fasting among women with breast cancer suggests that fasting
Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models. [2023]Accumulating evidence indicates that obesity with its associated metabolic dysregulation, including hyperinsulinemia and aberrant circadian rhythms, increases the risk for a variety of cancers including postmenopausal breast cancer. Caloric restriction can ameliorate the harmful metabolic effects of obesity and inhibit cancer progression but is difficult to implement and maintain outside of the clinic. In this study, we aim to test a time-restricted feeding (TRF) approach on mouse models of obesity-driven postmenopausal breast cancer. We show that TRF abrogates the obesity-enhanced mammary tumor growth in two orthotopic models in the absence of calorie restriction or weight loss. TRF also reduces breast cancer metastasis to the lung. Furthermore, TRF delays tumor initiation in a transgenic model of mammary tumorigenesis prior to the onset of obesity. Notably, TRF increases whole-body insulin sensitivity, reduces hyperinsulinemia, restores diurnal gene expression rhythms in the tumor, and attenuates tumor growth and insulin signaling. Importantly, inhibition of insulin secretion with diazoxide mimics TRF whereas artificial elevation of insulin through insulin pumps implantation reverses the effect of TRF, suggesting that TRF acts through modulating hyperinsulinemia. Our data suggest that TRF is likely to be effective in breast cancer prevention and therapy.
Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. [2019]We studied the effects of short-term dietary restriction on the survival of 3-4-month-old tumor-free and tumor-bearing Fisher rats. The diet-restricted food regimen consisted of alternate day ad libitum feeding followed by alternate day fasting. Diet-unrestricted control rats were fed ad libitum daily. Six tumor-free rats on the diet-restricted regimen compensated for the dietary restriction by an increase in food consumption during the alternate feeding days, and lost an average of only 2-3% of their weight in 13 days. Six tumor-free rats on a daily ad libitum feeding regimen gained an average of 6.8% in 15 days. The above dietary-restricted regimen was initiated 1 week before 24 rats were inoculated intraperitoneally with 15 million Mat 13762 ascites tumor cells. Sixteen of 24 (66.7%) diet-restricted tumor-bearing hosts and 5/24 (20.8%) diet-unrestricted tumor-bearing hosts survived at 9 days after tumor inoculation (p less than 0.005). Twelve of 24 (50%) diet-restricted tumor-bearing hosts, and 3 of 24 (12.5%) diet-unrestricted tumor-bearing hosts, survived at 10 days after tumor inoculation (p less than 0.025). Thus, the survival of tumor-bearing rats was enhanced by short-term relatively mild dietary restrictions. We suggest that relatively mild dietary restrictions should be included in clinical trials designed to inhibit cancer growth and enhance the survival of human cancer patients.
Effects of 4- and 6-h Time-Restricted Feeding on Weight and Cardiometabolic Health: A Randomized Controlled Trial in Adults with Obesity. [2022]Time-restricted feeding (TRF) regimens have grown in popularity; however, very few studies have examined their weight-loss efficacy. We conducted the first human trial (Clinicaltrials.gov NCT03867773) to compare the effects of two popular forms of TRF (4 and 6 h) on body weight and cardiometabolic risk factors. Adults with obesity were randomized to 4-h TRF (eating only between 3 and 7 p.m.), 6-h TRF (eating only between 1 and 7 p.m.), or a control group (no meal timing restrictions). After 8 weeks, 4- and 6-h TRF produced comparable reductions in body weight (∼3%), insulin resistance, and oxidative stress, versus controls. Energy intake was reduced by ∼550 kcal/day in both TRF groups, without calorie counting. These findings suggest that 4- and 6-h TRF induce mild reductions in body weight over 8 weeks and show promise as interventions for weight loss. These diets may also improve some aspects of cardiometabolic health.
Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. [2020]Time restricted feeding (TRF) mitigates the high-fat diet-enhanced mammary tumorigenesis in a MMTV-PyMT breast cancer model.
Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. [2022]Diet and lifestyle produce major effects on tumour incidence, prevalence, and natural history. Moderate dietary restriction has long been recognised as a natural therapy that improves health, promotes longevity, and reduces both the incidence and growth of many tumour types. Dietary restriction differs from fasting or starvation by reducing total food and caloric intake without causing nutritional deficiencies. No prior studies have evaluated the responsiveness of malignant brain cancer to dietary restriction. We found that a moderate dietary restriction of 30-40% significantly inhibited the intracerebral growth of the CT-2A syngeneic malignant mouse astrocytoma by almost 80%. The total dietary intake for the ad libitum control group (n=9) and the dietary restriction experimental group (n=10) was about 20 and 13 Kcal x day(-1), respectively. Overall health and vitality was better in the dietary restriction-fed mice than in the ad libitum-fed mice. Tumour microvessel density (Factor VIII immunostaining) was two-fold less in the dietary restriction mice than in the ad libitum mice, whereas the tumour apoptotic index (TUNEL assay) was three-fold greater in the dietary restriction mice than in the ad libitum mice. CT-2A tumour cell-induced vascularity was also less in the dietary restriction mice than in the ad libitum mice in the in vivo Matrigel plug assay. These findings indicate that dietary restriction inhibited CT-2A growth by reducing angiogenesis and by enhancing apoptosis. Dietary restriction may shift the tumour microenvironment from a proangiogenic to an antiangiogenic state through multiple effects on the tumour cells and the tumour-associated host cells. Our data suggest that moderate dietary restriction may be an effective antiangiogenic therapy for recurrent malignant brain cancers.
Chronic dietary restriction influences tumor metastasis in the rat: parametric considerations. [2007]Chronic dietary restriction is a well-documented means of inhibiting tumor growth. This study examines the effects of chronic dietary restriction on tumor metastasis in the rat. We investigate the effect of 1) the degree of food restriction, 2) the effect of preexposure to food restriction, and 3) the duration of food restriction after tumor inoculation on tumor metastasis. We also compare two methods of dietary restriction: 1) the time that food is available and 2) the amount of food available. Our findings demonstrate that rats restricted to 50% of ad libitum diet for one week before inoculation with MADB106 tumor cells and for three weeks after inoculation exhibit a significant (p