Pilot Study of Time Restricted Feeding as a Weight Loss Intervention

The circadian timing of energy intake (EI) has emerged as a key factor in the regulation of
body weight. Studies have suggested that eating meals later in the evening or during the
biological night when the circadian system is promoting sleep adversely influences the
success of weight loss therapy. In contrast, restricting EI to a short window during waking
hours and extending the length of the overnight fast (i.e., time restricted feeding, TRF) may
be a practical and useful strategy for promoting weight loss and weight maintenance. However,
potential benefits of adding TRF to a weight loss program have yet to be evaluated in a
well-controlled clinical study. The overall objective of this proposal is to provide a
foundation to inform the design of a future large-scale trial to evaluate the efficacy of TRF
in generating weight loss. The investigators overall hypothesis is that feasibility,
adherence, and acceptability of a weight loss intervention using TRF in the setting of a
reduced calorie diet (RCD) - RCD+TRF - will be similar to compliance with an intervention
using a reduced calorie diet alone (RCD), suggesting acceptability for a future large-scale
trial. In this 12-week pilot and feasibility study, 30 overweight and obese individuals will
be randomized 1:1 to RCD+TRF (EI restricted to a 10-hour window starting 1 hour from habitual
waking time) or standard RCD (no restriction on feeding duration). Additional follow-up will
occur at 6 months to collect pilot data on weight maintenance. Measures include feasibility,
acceptability and adherence to the interventions, body weight, body composition (Dual-energy
X-ray absorptiometry (DXA)), EI (smart phone application), physical activity (PA,
accelerometery), glucose variability (continuous glucose monitoring, CGM), sleep
(questionnaires and polysomnography), and nocturnal substrate metabolism (room calorimetry).
The specific aims (SA) are as follows:

Specific Aim 1a. To evaluate the feasibility and acceptability of a 12-week TRF intervention
compared to a standard dietary weight loss intervention (i.e. RCD). Feasibility of enrollment
and retention, and acceptability of the intervention will be assessed in adults with obesity
meeting inclusion/exclusion criteria proposed for the future large-scale trial. The
investigators will assess adherence to the weight loss programs, as measured objectively with
a novel smartphone application and verified with CGM data, and subjectively with the use of
questionnaires.

Specific Aim 1b. To assess the efficacy of RCD+TRF compared to RCD alone in producing weight
loss at 12 weeks and reducing the risk of weight regain after 6 months of follow-up.

Inclusion Criteria:

- Adult males and females with a BMI of 27-45 kg/m2 and weight stable over the previous
6 months;

- Age, 18-50 years old;

- Passing medical and physical screening, and analysis of blood and urine screening
samples;

- Typical eating duration >12 hours per day (assessed by questionnaires);

- Own a smartphone

Exclusion Criteria:

- Pregnancy or lactation for women (women who are >6 months postpartum with no plans of
becoming pregnant in the next year and who are not currently lactating can be
included; oral contraceptives will be allowed if medication has been consistent for
the prior 6 months)

- Postmenopausal women (menopausal status will be assessed during the history and
physical, with requirement of self-reported regular menstrual cycles for the last
year; women who have undergone hysterectomy but with ovaries in place who continue to
have regular menstrual symptoms can be included)

- Being considered unsafe to participate as determined by the study physician;

- History of cardiovascular disease, diabetes, uncontrolled hypertension, untreated
thyroid, renal, hepatic diseases, dyslipidemia or any other medical condition
affecting weight or lipid metabolism;

- History of human immunodeficiency virus or hepatitis B or C (self-report);

- Taking medications affecting weight or energy intake/energy expenditure in the last 6
months, including weight loss medications, antipsychotic drugs or other medications as
determined by the study physician;

- Having abnormal blood chemistry (eGFR<45mL/min, AST or ALT >3 times the upper limit of
normal) or as deemed significant by the study physician;

- Being a smoker or having been a smoker in the 3 months prior to their screening visit;

- Working night shifts;

- Extreme early or extreme late chronotype as determined by the Munich Chronotype
questionnaire37;

- Night eating syndrome (at least 25% of food intake is consumed after the evening meal
and/or at least two episodes of nocturnal eating per week) as assessed with meal
pattern assessment questionnaire;

- For participants completing the PSG studies, greater than moderate sleep apnea (score
high risk ≥ 2 or more categories on the Berlin Questionnaire). Participants completing
the primary weight loss intervention will not be excluded based on Berlin OSA risk
scores.

- For participants completing the PSG studies, use of medications affecting sleep
(benzodiazepines and other sleep aids, as determined by study physician). Participants
completing the primary weight loss intervention will not be excluded based on use of
medications affecting sleep.