||1R01CA258222-01 Interpret this number
||Cedars-Sinai Medical Center
||Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
Combining fasting with chemotherapy can cause complete tumor regression in animal models. Acute fasting is
thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy
cells by increasing stress resistance—a phenomenon known as the Differential Stress Sensitization theory.
However, the potential risks of extended caloric restriction hamper clinical implementation. Time-restricted eating
(TRE) is a promising alternative, which involves eating within a period of 10 hours or less, followed by fasting for
at least 14 hours daily. Because of its simplicity, TRE may be more sustainable. Moreover, our pilot data suggest
that TRE has several anti-cancer effects: it decreases IGF-1 levels, reduces oxidative stress, upregulates
antioxidant defenses, and enhances autophagy. We propose to conduct the first clinical trial of TRE in cancer
patients undergoing active treatment, as well as the largest randomized controlled trial of any form of intermittent
fasting in cancer patients. We will focus on rectal cancer because it is one of only a couple cancers where tumor
size and characteristics can be measured before and after treatment. We will enroll 300 newly diagnosed
localized rectal cancer patients (stage II-III) aged ≥18 (BMI ≥ 18.5 kg/m2). All participants will receive the standard
of care during oncological treatment at Cedars-Sinai Medical Cancer (Los Angeles, CA) or the University of
Alabama O’Neal Comprehensive Cancer Center (Birmingham, AL) and be randomized to one of two eating
schedules: (1) control schedule: 12-hour or longer daily eating period; (2) TRE: 8-hour daily eating period (16
hours of daily fasting). Participants will be counseled to maintain their weight. All endpoints will be measured at
least three times: at diagnosis prior to the onset of chemoradiation (baseline), after chemoradiation treatment,
and at tumor resection (post-intervention). Our primary aim is to determine how TRE affects clinical outcomes,
including treatment-related adverse effects (toxicity index based on CTCAE v.5), patient-reported outcomes
(PRO-CTCAE) and quality of life (EORTC QLQ-C30), and clinical (cCR) and pathological (pCR) complete
response rates. Aim 2 tests the Differential Stress Sensitization Theory—the first complete test of this theory in
humans. We test whether TRE acts through the IGF-1 pathway to increase stress resistance in healthy cells
(DNA damage and antioxidant defenses as measured by gamma-H2AX and total antioxidant capacity,
respectively) and enhance tumor cell death (apoptosis and autophagy as measured by activated caspase-3 and
LC3-I/LC3-II, respectively). Aim 3 compares longitudinal changes in mood, social functioning, sleep, diet, and
daily physical activity across intervention arms (control vs. TRE) and explore how these changes interact with
intervention arms to predict clinical outcomes. We expect this innovative trial will help improve cancer treatment
outcomes and reshape the standard of care for cancer patients.
Use of continuous glucose monitoring in obesity research: A scoping review.
, Salvy S.J.
, Wee C.P.
, Naguib M.
, Raymond J.K.
, Fox D.S.
, Vidmar A.P.
Obesity research & clinical practice, 2021 Sep-Oct; 15(5), p. 431-438.