Time-Restricted Eating for Prostate Cancer Survivorship

(ADRIAN Trial)

Overseen By Amber Kleckner, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Maryland, Baltimore

Must be taking: Hormone therapy

Disqualifiers: Chemotherapy, Radiation, Underweight, Surgery, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Frailty is one of the main reasons older adults lose independence. Frailty describes a reduced ability to withstand stress on the physiological scale, or a reduced physiological reserve. The theory is that entrainment of circadian rhythm via time-restricted eating will improve the body's ability to predict energy supply and demand, and therefore enable the body to allocate more resources to anabolic processes and promote resilience to cancer treatment, thereby preventing the progression of frailty. A total of 30 individuals over 55 years old undergoing ADT therapy for prostate cancer will be recruited. Participants will be randomized 1:1 to a 12-week TRE intervention or a time-unrestricted nutrition control intervention. At baseline and post-intervention, Fried's Frailty Index will be used to assess frailty, and a novel set of five physiological responsiveness measures will be used to assess physiological responsiveness-1) lying-to-standing blood pressure, 2) heart rate variability, 3) oral glucose tolerance test, 4) 24-hour circadian cortisol rhythm, and 5) usual vs. fast gait speed. These data will allow assessment of 1) the feasibility of TRE among patients with prostate cancer during ADT treatment with the ultimate goal of optimizing an intervention to prevent the progression of frailty, and 2) the effects of TRE vs. control on frailty and physiological responsiveness.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have any contraindications to the nutrition intervention due to medication requirements, you may not be eligible to participate.

What data supports the effectiveness of the treatment Time-restricted eating for prostate cancer survivorship?

Research on mice suggests that intermittent fasting, a form of time-restricted eating, may help manage prostate cancer by potentially prolonging survival, although results are not definitive. Additionally, combining fasting with other therapies has shown promise in improving treatment outcomes for other types of cancer. ^{1 2 3 4 5}

Is time-restricted eating safe for humans?

Research on time-restricted eating (TRE) and similar fasting methods in humans is limited, but studies in animals suggest these methods are generally safe. In humans, TRE has been used by athletes without negative effects on performance, indicating it may be safe for healthy individuals. ^{1 6 7 8 9}

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

Time-restricted eating (TRE) is unique because it focuses on limiting the hours of food intake each day, rather than reducing the amount of food or using medication. This approach may be easier for some people to follow compared to strict calorie restriction and could potentially influence cancer growth by affecting hormone levels like insulin and IGF-1, which are linked to cancer progression. ^{1 2 3 6 10}

Research Team

Amber Kleckner, PhD

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for individuals over 55 with prostate cancer undergoing ADT therapy who can follow the study procedures and speak/read English. It's not for those who already eat within a 10-hour window, have upcoming surgery, contraindications to diet changes (like type 1 diabetes), are on artificial nutrition, underweight, or have had significant weight loss recently.

Inclusion Criteria

Speak and/or read English

Be able and willing to adhere to the study procedures

I have been diagnosed with prostate cancer.

Exclusion Criteria

I have unintentionally lost more than 10 pounds in the past year.

Already eat all their food in a window that is 10 h or shorter on most (6/7) days of the week

Be underweight (≤18.5 kg/m2)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to a 12-week time-restricted eating (TRE) intervention or a time-unrestricted nutrition control intervention

12 weeks

Regular meetings with a nutritionist

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of frailty and physiological responsiveness

4 weeks

Treatment Details

Interventions

• Time-restricted eating

Trial Overview The study tests if time-restricted eating can help older adults better handle stress from frailty and prostate cancer treatment. Participants will either follow a strict eating schedule or their usual habits for 12 weeks while researchers measure changes in frailty and physiological responses like blood pressure and glucose tolerance.

Participant Groups

Group I: Time-restricted eating Experimental Treatment 2 Interventions

Participants will meet with a nutritionist to discuss dietary recommendations for patients with prostate cancer undergoing ADT. Participants will self-select a 10-hour window in which to consume all food and beverages (with the exception of black coffee and unsweetened tea in the mornings; water is okay at all times).

Group II: Unrestricted eating Active Control 1 Intervention

Participants will meet with a nutritionist to discuss dietary recommendations for patients with prostate cancer undergoing ADT. Participants will try to follow recommendations will no suggestion for meal timing.

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

In a pilot study involving 105 male SCID mice with prostate cancer, intermittent fasting regimens showed non-significant trends toward improved survival compared to a control group, suggesting potential benefits of fasting in cancer management.

Mice on certain fasting diets had significantly lower body weights and IGF-1 levels, indicating that these dietary interventions may influence cancer growth mechanisms, although no significant survival differences were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice. Buschemeyer, WC., Klink, JC., Mavropoulos, JC., et al.[2010]

In a study involving 100 mice with prostate cancer, intermittent fasting (IF) did not improve survival rates or delay tumor growth compared to a regular diet, indicating that this approach may not be effective for cancer treatment in this model.

Despite the lack of survival benefits, mice undergoing IF showed significantly higher levels of IGF-1, suggesting that metabolic changes during fasting may counteract potential anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. Thomas, JA., Antonelli, JA., Lloyd, JC., et al.[2010]

In a study involving 160 male SCID mice with prostate cancer, a 20% carbohydrate diet significantly slowed tumor growth compared to a western diet, suggesting dietary modifications may impact cancer progression.

While survival rates did not significantly differ among the various carbohydrate-restricted diets, there was a non-significant trend indicating improved survival for those on carbohydrate-restricted diets compared to the western diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. Caso, J., Masko, EM., Ii, JA., et al.[2021]

Preliminary findings indicate that combining intermittent fasting or a fasting-mimicking diet with endocrine therapy may enhance the effectiveness of treatment for hormone receptor-positive breast cancer.

This combination approach could also help in reducing side effects associated with the endocrine therapy, suggesting a potential strategy for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting May Complement Endocrine Therapy. [2021]

A systematic review of 20 randomized controlled trials found that diet interventions, either alone or combined with exercise, can lead to significant weight loss in men treated for prostate cancer, with weight loss ranging from 0.8 kg to 6.1 kg.

Exercise alone did not result in weight loss, as most trials focused on improving fitness and quality of life rather than reducing body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of dietary and exercise interventions on body weight in prostate cancer patients: a systematic review. Mohamad, H., McNeill, G., Haseen, F., et al.[2022]

In a 4-week study with 24 male mice, the modified alternate-day fasting (ADF-100%) regimen significantly reduced prostate cell proliferation by 49% and T-cell proliferation by 30%, indicating a potential decrease in cancer risk.

The ADF-100% group also showed a 40% reduction in circulating insulin-like growth factor-1 (IGF-1) levels, which is associated with lower cancer risk, while other modified ADF regimens (ADF-25% and ADF-50%) did not produce similar effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose effects of modified alternate-day fasting regimens on in vivo cell proliferation and plasma insulin-like growth factor-1 in mice. Varady, KA., Roohk, DJ., Hellerstein, MK.[2015]

Intermittent fasting through time-restricted feeding (TRF) did not hinder muscle growth or performance in resistance-trained females, showing that similar gains can be achieved regardless of feeding schedule, as long as energy and protein intake are maintained.

Participants on TRF experienced a significant reduction in fat mass compared to those on a control diet, suggesting that TRF may be beneficial for fat loss without compromising muscle adaptations during resistance training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted feeding plus resistance training in active females: a randomized trial. Tinsley, GM., Moore, ML., Graybeal, AJ., et al.[2023]

A 4-week study on trained male endurance runners showed that a 16/8 time-restricted feeding (TRF) pattern led to a significant decrease in fat mass without affecting fat-free mass or running performance.

While the TRF group experienced lower carbon dioxide production and blood lactate levels during exercise, their 10 km time trial performance remained unchanged compared to those on a normal diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four Weeks of 16/8 Time Restrictive Feeding in Endurance Trained Male Runners Decreases Fat Mass, without Affecting Exercise Performance. Tovar, AP., Richardson, CE., Keim, NL., et al.[2021]

Modified alternate-day fasting (ADF) significantly reduces cell proliferation rates in various tissues, regardless of whether the diet is low-fat or high-fat, suggesting its potential as a cancer prevention strategy.

In a 4-week study with male mice, both ADF groups showed similar reductions in T-cell proliferation and decreased plasma insulin-like growth factor-1 levels, indicating that ADF can be effective across different dietary fat intakes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice. Varady, KA., Roohk, DJ., Bruss, M., et al.[2009]

In a study of 45 elderly men undergoing radiotherapy for prostate cancer, the antifermentative diet led to a significant decrease in energy and nutrient intake, including essential vitamins and minerals, during treatment.

Body composition was adversely affected by the diet, with participants experiencing reductions in body weight, arm circumference, and other measurements by the end of radiotherapy, indicating potential negative impacts on overall health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the antifermentative diet during radiotherapy for prostate cancer in elderly, SÃO Paulo, Brazil. de Oliveira Pedron, ÉL., de Cássia de Aquino, R., Borin da Silva, C.[2021]

References

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

Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice. [2010]

2. England pubmed.ncbi.nlm.nih.gov

Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. [2010]

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

The effect of carbohydrate restriction on prostate cancer tumor growth in a castrate mouse xenograft model. [2021]

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

Fasting May Complement Endocrine Therapy. [2021]

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

The effect of dietary and exercise interventions on body weight in prostate cancer patients: a systematic review. [2022]

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

Dose effects of modified alternate-day fasting regimens on in vivo cell proliferation and plasma insulin-like growth factor-1 in mice. [2015]

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

Time-restricted feeding plus resistance training in active females: a randomized trial. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Four Weeks of 16/8 Time Restrictive Feeding in Endurance Trained Male Runners Decreases Fat Mass, without Affecting Exercise Performance. [2021]

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

Alternate-day fasting reduces global cell proliferation rates independently of dietary fat content in mice. [2009]

10. Germany pubmed.ncbi.nlm.nih.gov

Impact of the antifermentative diet during radiotherapy for prostate cancer in elderly, SÃO Paulo, Brazil. [2021]