Remote Time-restricted EAting DeliverY

Study Overview
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Brief Summary
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This study will evaluate the implementation and effectiveness of free-living TRE on biological and behavioural breast cancer risk factors.

Detailed Description
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TRE is an eating pattern where individuals consume ad libitum energy intake within a set window of time, commonly 8 hours, which induces a fasting window of 16 hours per day (i.e., 16:8 TRE). TRE is a simple and accessible lifestyle intervention with high adherence potential that may target both biological and behavioural mechanisms of breast cancer risk.

Official Title
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Proof-of-Concept of Time-Restricted Eating as a Novel Lifestyle Intervention for Breast Cancer Prevention

Conditions
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Metabolic Disturbance

Intervention / Treatment
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* Behavioral: Standardized TRE Protocol
* Behavioral: Personalized TRE Protocol
* Behavioral: External Support for TRE
* Behavioral: Peer Support for TRE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females No cancer history ≥50 years old Have metabolic dysfunction (defined as self-reported diagnosis of pre-diabetes, type 2 diabetes, or at least moderate Canadian diabetes risk (CANRISK) score) Access to an Ontario Lifelabs location Owns a smartphone with Bluetooth capability with Apple or Android operating system Exclusion Criteria: Type 1 diabetes Taking exogenous insulin, sulfonylureas, or GLP-1 receptor agonists Self-reported history of an eating disorder BMI <18.5 kg/m Working night or rotating shifts Eating window <12 hours or consistently eating less than 3 meals/day in the past 3 months Major dietary changes within the past 3 months (i.e. calorie counting, ketogenic diet)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Standardized TRE protocol + External Support<br>Participants will be asked to follow a standardized 16:8 TRE protocol with an 11 am to 7 pm eating window for 16 weeks. Participants receive support to follow the TRE intervention from the study team which will include an initial consultation with a registered dietitian and ongoing tailored feedback via brief support calls from study staff at weeks 1, 3, 6, and 12. | Behavioral: Standardized TRE Protocol<br>* A standardized 16:8 TRE protocol with an 11 am to 7 pm eating window.<br>Behavioral: External Support for TRE<br>* External support (from study staff) that includes consultation with a registered dietitian and ongoing tailored feedback via support calls at weeks 1, 3, 6, and 12.<br>|
| Experimental: Standardized TRE protocol + Peer Support<br>Participants will be asked to follow a standardized 16:8 TRE protocol with an 11 am to 7 pm eating window for 16 weeks. Each participant will be matched with another participant in the same group to provide peer-based support to adhere to TRE. Study staff will introduce pairs and provide an introduction to TRE and then pairs will meet by phone/video at weeks 1, 3, 6, and 12 at a minimum, with additional contact encouraged. | Behavioral: Standardized TRE Protocol<br>* A standardized 16:8 TRE protocol with an 11 am to 7 pm eating window.<br>Behavioral: Peer Support for TRE<br>* Matched pairs will meet by phone/video at weeks 1, 3, 6, and 12.<br>|
| Experimental: Personalized TRE protocol + External Support<br>Participants will be asked to follow TRE for 16 weeks with a protocol that is personalized to their preferences within the following pre-specified rules: 1) 8-10 hour eating window; 2) self-selected eating window start time as long as it ends ≥3h before bedtime; 3) if days off are required, aim to do so after following TRE for ≥5 successive days each week. Participants receive support to follow the TRE intervention from the study team which will include an initial consultation with a registered dietitian and ongoing tailored feedback via brief support calls from study staff at weeks 1, 3, 6, and 12. | Behavioral: Personalized TRE Protocol<br>* A personalized TRE protocol following pre-specified rules: 1) 8-10 hour eating window; 2) self-selected eating window start time as long as it ends ≥3h before bedtime; 3) if days off are required, aim to do so after following TRE for ≥5 successive days each week.<br>Behavioral: External Support for TRE<br>* External support (from study staff) that includes consultation with a registered dietitian and ongoing tailored feedback via support calls at weeks 1, 3, 6, and 12.<br>|
| Experimental: Personalized TRE protocol + Peer Support<br>Participants will be asked to follow TRE for 16 weeks with a protocol that is personalized to their preferences within the following pre-specified rules: 1) 8-10 hour eating window; 2) self-selected eating window start time as long as it ends ≥3h before bedtime; 3) if days off are required, aim to do so after following TRE for ≥5 successive days each week. Each participant will be matched with another participant in the same group to provide peer-based support to adhere to TRE. Study staff will introduce pairs and provide an introduction to TRE and then pairs will meet by phone/video at weeks 1, 3, 6, and 12 at a minimum, with additional contact encouraged. | Behavioral: Personalized TRE Protocol<br>* A personalized TRE protocol following pre-specified rules: 1) 8-10 hour eating window; 2) self-selected eating window start time as long as it ends ≥3h before bedtime; 3) if days off are required, aim to do so after following TRE for ≥5 successive days each week.<br>Behavioral: Peer Support for TRE<br>* Matched pairs will meet by phone/video at weeks 1, 3, 6, and 12.<br>|
| No Intervention: Control Group<br>Participants will be asked to maintain their usual diet and physical activity patterns for 16 weeks. They will receive the same number and timing of calls from study staff as the other groups (at randomization, 1, 3, 6, 12 weeks). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to TRE for the 16-week intervention | Assessed daily through twice daily automated text messages asking participants to respond with what time they started and stopped eating that day. | 16-week average | 
| Hemoglobin A1c | Collected via venipuncture | 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HOMA-IR | Homeostatic Model Assessment for Insulin Resistance calculated as fasting glucose in mmol/l*fasting insulin in μU/ml/22.5 | 16 Weeks | 
| Free-living glucose control | Participants will be provided with a Dexcom G6 continuous glucose monitor transmitter and sensor. This data will be evaluated as the 5-day average of: 24-hour, daytime, and nocturnal glucose concentration, time in hyper, normo and hypoglycemia, and glycemic variability | 16 Weeks | 
| C-Reactive Protein | Measured via venipuncture and core lab lab analysis | 16 Weeks | 
| Lipid profile | Measured via venipuncture and core lab lab analysis | 16 Weeks | 
| Body weight | Measured via Fitbit Aria Air scale at baseline and 16-weeks but also once per week to evaluate trajectory of change | 16 Weeks | 
| Waist circumference | Measured via provided circumference measuring tape as the average of 2 measurements | 16 weeks | 
| Blood Pressure | Participant will be provided with a Bios 3al1-3e blood pressure measuring device. After 5 minutes of quiet seated rest, blood pressure will be measured 6 times, 60 seconds apart in a standardized seated position with the average of the 2nd through 6th measurement used. | 16 Weeks | 
| 10-year cardiovascular disease risk | Calculated via both the Framingham and Reynolds 10-year CVD risk scores using measured collected for study purposes (i.e., age, total cholesterol, HDL, systolic blood pressure, smoking status, C-reactive protein, family history of heart disease). | 16 Weeks | 
| Metabolic syndrome (NCEP/ATP III criteria) | As defined by the NCEP/ATP III criteria using measurements taken using provided study tools | 16 Weeks | 
| Metabolic syndrome z-score | As defined by the NCEP/ATP III criteria and age and ethnic specific calculations | 16 Weeks | 
| Alanine Aminotransferase | Measured via venipuncture and core lab lab analysis | 16 Weeks | 
| TRE acceptability and appropriateness | Evaluated via an 'End of Study Survey' (including a Diet Satisfaction Score Tool and acceptability questions) and semi-structured qualitative interviews | 16 Weeks | 
| TRE Adoption | Evaluated as uptake of each delivery model, defined as adherence to the intervention touch points (i.e., external support: support calls with staff; peer support: number of peer interactions; both: response rate to adherence). | 16 Weeks | 
| Cost of intervention delivery | Intervention costs will be evaluated and averaged per participant from the time required for intervention phone calls, scheduling, and technical support for adherence app by the study staff according to hourly rates of pay. | 16 Weeks | 
| TRE Sustainability | Evaluated via participant self-report of continued TRE post-intervention | 1, 2, 3, and 4 months post intervention period | 
| TRE Adverse Events | Measured via experience of selected relevant Common Terminology Criteria for Adverse Events (CTCAE v5) with additional questions about duration and change in the revised 18-item version of the Three-Factor Eating Questionnaire (aka Eating Inventory) | 16 Weeks | 
| Health-related quality of life | Measured by the RAND-36 Physical Component Summary. Physical component summary of the RAND-36 questionnaire (minimum = 0, maximum = 50, a higher score is a better outcome) | 16 Weeks | 
| Sleep duration | Measured via FitBit Inspire 2 as 7-day average | 16 Weeks | 
| Sedentary time | Measured via FitBit Inspire 2 as 7-day average | 16 Weeks | 
| Physical activity | Measured via FitBit Inspire 2 as 7-day average | 16 Weeks |