Protocol for the CLOCKS study: A 4-arm randomized controlled trial testing the independent and combined effects of 2 chronotherapies-early time-restricted eating and daytime bright light therapy-in adults with type 2 diabetes.

Disruption of circadian rhythms worsens glycemic control and cardiovascular health. Conversely, evidence suggests that optimizing circadian rhythms by eating earlier in the day, practicing intermittent fasting, and/or getting sufficient sunlight or bright light during the daytime improves cardiometabolic health. Here, we describe the protocol for a 2 × 2 randomized controlled trial testing whether two chronotherapies-early time-restricted eating (eTRE) and/or daytime bright light therapy (BLT)-can improve glycemic control, diurnal rhythms, and overall health in adults with type 2 diabetes (T2D). We will randomize 344 adults with insulin-independent T2D to 1 of 4 groups: (1) control, (2) eTRE, (3) daytime BLT, or (4) eTRE + daytime BLT. Participants in the eTRE groups will eat within an 8-hour window ending by 17:00, while those in the BLT group will receive bright light for 90 min/day before 15:00 and use blue-light-blocking glasses and blackout curtains at night. The intensive phase of the intervention is 16 weeks, with follow-up at the 1-year mark. The primary outcome is glycemic control as measured by HbA1c and 24-hour glucose, supplemented by additional assessments of glucose metabolism. Secondary outcomes are the diurnal melatonin and cortisol rhythms and the diurnal variation in glucose uptake. Tertiary outcomes include body mass, body composition, resting energy expenditure, cardiovascular risk factors, sleep parameters, quality of life, and psychological health. To our knowledge, this is the largest study to date of TRE in people with T2D and the largest study to test whether daytime bright light therapy can improve cardiometabolic health. Trial Registration: This trial was registered at clinicaltrials.gov (NCT04155619).