Time-Restricted Eating for Cancer

Overseen By Eleah Stringer, MSc, RD, CSO

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must not be taking: Food-required medications

Disqualifiers: Diabetes, Pregnancy, Anti-lymphoma therapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3-6 months

75 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if time restricted eating (TRE), a form of intermittent fasting, can impact health outcomes in patients with chronic lymphocytic leukemia (CLL). The main questions it aims to answer are: * In patients with CLL, is there a decrease or stabilization in cancer cell counts associated with TRE compared to baseline? * Is there a decrease in immune cell autophagy (a cellular recycling process) activity associated with TRE compared to baseline? * Does adherence to a TRE regimen improve patient experience and quality of life? Immune cell autophagy activity in cancer patients will be compared to a subset of control participants without cancer. Participants will: * Adhere to a 16/8 fasting regimen, which involves eating as normal for 8 hours per day and fasting (only consuming water, black coffee or black tea) for the remaining 16 hours. They will follow this intervention for their choice of either 3 or 6 months. * Complete monthly blood collections * Complete weekly journal entries to record weekly weight and timing of first and last daily meals * Complete weekly safety check-ins with a study team member for the first 4 weeks of the study and then bi-weekly thereafter * Complete 3 quality of life questionnaires * Provide 3 stool samples (optional component of study) * Complete an end of study interview (optional component of study)

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 on medications that must be taken with food during the fasting period.

What data supports the effectiveness of the treatment Time-Restricted Eating for cancer?

Research in mice has shown that time-restricted eating can reduce the spread of certain types of cancer, like breast cancer and lung cancer, especially when combined with a high-fat diet. However, the effects in humans are still unclear due to mixed results in studies. ^{1 2 3 4 5}

Is time-restricted eating safe for humans?

Time-restricted eating (TRE) has been studied in humans and animals, showing beneficial health effects like improved metabolism and weight management. While specific safety data for cancer patients is limited, TRE is generally considered safe for humans based on existing studies. ^{3 4 5 6 7}

How is time-restricted eating different from other cancer treatments?

Time-restricted eating (TRE) is unique because it focuses on limiting the hours during which food is consumed each day, aligning eating patterns with the body's natural circadian rhythms. Unlike traditional cancer treatments that often involve medication or surgery, TRE is a dietary approach that may help improve metabolic health and potentially enhance cancer survival by reducing chronodisruption (misalignment of the body's internal clock with external cues). ^{6 8 9 10 11}

Research Team

Eleah Stringer, MSc, RD, CSO

Principal Investigator

BC Cancer

Eligibility Criteria

This trial is for patients with chronic lymphocytic leukemia (CLL) or other hematological malignancies like lymphoma. Participants should be willing to follow a 16/8 fasting regimen, provide blood samples, and complete questionnaires. They must not have conditions that make fasting unsafe.

Inclusion Criteria

Experimental Participants: Diagnosis of CLL or SLL, Age 18-85, Peripheral blood lymphocytes >20 x 10^9/L, Hemoglobin >90g/L, Platelets >90 x 10^9/L, BMI of >=20kg/m2, ECOG Performance Status >=2; not following any form of IF for 4 months prior to study

Exclusion Criteria

Pregnant or breastfeeding

BMI drop to < 18.5kg/m2 at any time during study

I have diabetes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants adhere to a 16/8 fasting regimen for either 3 or 6 months, complete monthly blood collections, weekly journal entries, and safety check-ins.

3-6 months

Weekly safety check-ins for the first 4 weeks, then bi-weekly; monthly blood collections

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up blood collection one month after completion of the TRE study period.

1 month

Optional End of Study Interview

Participants may complete an optional end of study interview to discuss their experience.

Treatment Details

Interventions

• Time-Restricted Eating

Trial Overview The study tests if time-restricted eating (TRE), an intermittent fasting method where participants eat normally for 8 hours and fast for the remaining 16 hours daily, affects cancer cell counts, immune cell autophagy activity, and improves quality of life in CLL patients.

Participant Groups

Group I: Experimental Group Experimental Treatment 1 Intervention

Research Design: A nonrandomized control design will be followed with a 4:1 ratio (experimental: control). The experimental arm will consist of patients with early stage CLL who are on surveillance (n=60). The control arm will consist of community members who do not have cancer (n=15). Participants will follow a fasting intervention of an 8-hour feeding window with a 16-hour fasting window for a minimum of 6/7 days per week for either 3 months (90 days) or 6 months (180 days) based on their preference. Participants with cancer will provide blood samples, stool samples (optional) and will complete journals, check ins, and quality of life surveys per the schedule outlined in section 5.7 as well as in the attached study protocol document in section 6. Upon completion of study, participants with cancer may also complete an optional end of study interview.

Group II: Control Group Active Control 1 Intervention

Research Design: A nonrandomized control design will be followed with a 4:1 ratio (experimental: control). The experimental arm will consist of patients with early stage CLL who are on surveillance (n=60). The control arm will consist of community members who do not have cancer (n=15). Participants will follow a fasting intervention of an 8-hour feeding window with a 16-hour fasting window for a minimum of 6/7 days per week for either 3 months (90 days) or 6 months (180 days) based on their preference. Participants with cancer will provide blood samples, stool samples (optional) and will complete journals, check ins, and quality of life surveys per the schedule outlined in section 5.7 as well as in the attached study protocol document in section 6. Upon completion of study, participants with cancer may also complete an optional end of study interview. Control participants will provide blood samples and weekly journals to serve as a control for autophagy flux analysis.

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

BC Cancer Foundation

Collaborator

Trials

20

Recruited

8,600+

Michael Smith Health Research BC

Collaborator

Trials

2

Recruited

480+

Findings from Research

This study is the first to evaluate the effects of time-restricted eating (TRE) on weight loss in a controlled manner, comparing it to a usual eating pattern (UEP) while ensuring both groups consumed the same number of calories and identical diets.

Participants aged 21-69 with prediabetes and obesity were monitored closely, allowing for a rigorous assessment of how meal timing impacts weight change without altering caloric intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Implementation of a Time-Restricted Eating Intervention in a Randomized, Controlled Eating Study. White, K., Wu, B., Pilla, SJ., et al.[2023]

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]

Time-restricted eating (TRE) has shown promising therapeutic effects in rodent studies, particularly in relation to body weight and metabolic health, but results in humans are inconsistent due to varying study designs and populations.

This review highlights the need for more standardized research on TRE in humans to better understand its effects and interactions with circadian biology, as well as to identify gaps in current knowledge for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex physiology and clinical implications of time-restricted eating. Petersen, MC., Gallop, MR., Flores Ramos, S., et al.[2023]

In a study involving 172 women undergoing chemotherapy, intermittent energy restriction (IER) showed a trend towards greater weight and body fat reduction compared to continuous energy restriction (CER), particularly after adjusting for body water.

While the overall incidence of severe chemotherapy toxicities was similar between IER and CER, there was a trend indicating fewer severe toxicities in the IER group during later cycles of treatment, suggesting IER may help reduce treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer. Harvie, M., Pegington, M., Howell, SJ., et al.[2022]

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]

Time-restricted eating (TRE) is a promising dietary approach that not only aids in weight management but also positively influences energy metabolism, gut microbiota, and overall homeostasis.

Chronodisruption, which occurs when our internal circadian rhythms are out of sync with external cues, is linked to serious health issues like metabolic disorders and cancer, highlighting the importance of aligning eating patterns with our biological clocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted eating for chronodisruption-related chronic diseases. Cheng, WY., Desmet, L., Depoortere, I.[2023]

In a study involving 15 men over 8 weeks, time-restricted eating (TRE) significantly altered 24-hour profiles of key metabolic markers, including insulin and triglycerides, suggesting potential benefits for metabolic health.

TRE also influenced the expression of genes related to circadian rhythms and transcriptional regulation in subcutaneous adipose tissue, indicating a mechanism by which TRE may improve metabolic function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity. Zhao, L., Hutchison, AT., Liu, B., 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 an 8-week study of time-restricted feeding (TRF) involving 32 women (13 premenopausal and 19 postmenopausal), both groups experienced similar weight loss of about 3.3% without any significant differences between them.

Both premenopausal and postmenopausal women showed reductions in fat mass, lean mass, fasting insulin, and oxidative stress markers, indicating that TRF can provide metabolic benefits regardless of menopausal status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in body weight and metabolic risk during time restricted feeding in premenopausal versus postmenopausal women. Cienfuegos, S., Gabel, K., Kalam, F., et al.[2023]

In a 12-week study involving 14 adults with obesity, time-restricted feeding (8-hour eating window) led to a significant weight loss of about 2 kg, indicating potential efficacy for weight management.

Despite the weight loss, the study found no significant changes in the diversity or composition of the gut microbiome, suggesting that time-restricted feeding may not impact gut health in terms of microbial diversity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study. Gabel, K., Marcell, J., Cares, K., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Design and Implementation of a Time-Restricted Eating Intervention in a Randomized, Controlled Eating Study. [2023]

2. 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]

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

Complex physiology and clinical implications of time-restricted eating. [2023]

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

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Time-restricted eating for chronodisruption-related chronic diseases. [2023]

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

Time-restricted eating alters the 24-hour profile of adipose tissue transcriptome in men with obesity. [2023]

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

Early time-restricted feeding improves high-density lipoprotein amount and function in nonhuman primates, without effects on body composition. [2023]

9. England pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Changes in body weight and metabolic risk during time restricted feeding in premenopausal versus postmenopausal women. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study. [2022]