Effects of Time-Restricted Fasting on the Postprandial Glycemic Responses

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical trial is to investigate whether fasting timing has a significant effect on postprandial glycemic responses in healthy adults. The main questions it aims to answer are: Whether fasting timing has a significant effect on postprandial insulin actions and plasma glucose concentration. Whether fasting timing could modulate the glycemic metabolome and circadian rhythms in healthy individuals. Participants will get the two interventions: No-dinner: breakfast at 7.30 a.m., lunch at 1.00 p.m. and no dinner; No-breakfast: no breakfast, lunch at 1.00 p.m. and dinner at 8.00 p.m.

Detailed Description
-----------------
A randomized, crossover study design is used with 2 intervention days and a 6-day washout period, to evaluate the effects of early and late fasting on postprandial glucose responses in healthy adults. Randomization was performed by the Fudan staff with a block size of 2 using a balanced design using computer-executed software. The primary endpoint is the fasting and postprandial blood glucose, insulin, and continuous glucose monitoring after fasting. Secondary endpoints include postprandial blood lipids, clock gene expressions in peripheral blood cells, and non-targeted postprandial plasma metabolome. The 2 intervention days include a no-breakfast day and a no-dinner day. The diets before, during, and after the intervention day was designed according to Dietary Guidelines for Chinese Residents (2022), and the energy distribution of three meals is 1:1:1, with the energy percentage of carbohydrate, protein, and fat being 55%, 15%, and 30%, respectively. The time of breakfast, lunch, and dinner is 7.30 a.m., 1.00 p.m., and 8.00 p.m., respectively. All participants are instructed to follow their natural dietary plans in the wash-out period, and the food intakes and sleep circle were recorded by a modified food frequency questionnaire (FFQ).

Official Title
-----------------
Effects of Time-Restricted Fasting on the Postprandial Glycemic Responses in Chinese Adults: A Randomized Crossover Study

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Behavioral: Consumption of lunch and dinner, with no breakfast
* Behavioral: Consumption of breakfast and lunch, with no dinner


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Both men and women are eligible. Age: 18-40 years old. Healthy adults: no history of diabetes mellitus, no use of hypoglycemic drugs, no insulin injection. All participants have a good sleep circle, with no somnipathy. Exclusion Criteria: Severe mental illness or other major medical comorbidities and autoimmune diseases (e.g., chronic renal failure, cardiovascular diseases, or cancer) Skipping breakfast or dinner more than 10 times within 6 months. Following a special diet, currently on weight loss medication, using sleeping medications. Pregnancy or to be pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A randomized, crossover study design uses two intervention days (a no-breakfast day and a no-dinner day) and a 6-day washout period.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No-breakfast<br>One-day meal plan with no breakfast. The dietary plan has been developed according to the Dietary Guidelines for Chinese Residents (2022), and the energy distribution of the two meals (lunch and dinner) is 1:1, with the energy percentage of carbohydrates, proteins, and fats being 55%, 15%, and 30%, respectively. The total daily calorie intake has been calculated based on the gender difference of the participants. Since the recommended daily calorie intake for males is 2000 kcal while for females it is 1600 kcal, each meal for males is designed to provide 667 kcal calories, comprising 92g carbohydrates, 22g fat, and 25g protein; each meal for females is designed to provide 533 kcal calories, comprising 73g carbohydrates, 18g fat, and 20g protein. The carbohydrates are sourced from buckwheat flour and mixed grain rice, which create similar glycemic indexes for each meal. Additionally, the one-day meal for both males and females includes 450g of vegetables and 320g of fruits. | Behavioral: Consumption of lunch and dinner, with no breakfast<br>* The day before intervention day, all participants will be provided with 3 nutritionally balanced meals which are designed by the investigators. On the no-breakfast intervention day, participants are instructed to fast and only be allowed to consume water until 1.00 p.m. and consume the above-designed lunch and dinner at 1.00 p.m. and 8.00 p.m. Additionally, all participants are informed that they are only allowed to consume water between meals and before receiving breakfast at 7.30 a.m. the following day.<br>|
| Experimental: No-dinner<br>One-day meal plan with no dinner. The dietary plan has been developed according to the Dietary Guidelines for Chinese Residents (2022), and the energy distribution of the two meals (breakfast and lunch) is 1:1, with the energy percentage of carbohydrates, proteins, and fats being 55%, 15%, and 30%, respectively. The total daily calorie intake has been calculated based on the gender difference of the participants. Since the recommended daily calorie intake for males is 2000 kcal while for females it is 1600 kcal, each meal for males is designed to provide 667 kcal calories, comprising 92g carbohydrates, 22g fat, and 25g protein; each meal for females is designed to provide 533 kcal calories, comprising 73g carbohydrates, 18g fat, and 20g protein. The carbohydrates are sourced from buckwheat flour and mixed grain rice, which create similar glycemic indexes for each meal. Additionally, the one-day meal for both males and females includes 450g of vegetables and 320g of fruits. | Behavioral: Consumption of breakfast and lunch, with no dinner<br>* The day before intervention day, all participants will be provided with 3 nutritionally balanced meals which are designed by the investigators. On the no-dinner intervention day, participants are instructed to consume the above-designed breakfast and lunch at 7.30 a.m. and 1.00 p.m., and no dinner. Additionally, all participants are informed that they are only allowed to consume water between meals and before receiving breakfast at 7.30 a.m. on the following day.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from fasting to postprandial postprandial blood glucose | The primary endpoint is fasting and postprandial blood glucose with hexokinase tests. | Blood samples collected before and after 2 hours at lunch on the no-breakfast day; blood samples collected before and after 2 hours at next day breakfast on the no-dinner day | 
| Change from fasting to postprandial insulin | Fasting and postprandial insulin will be tested by ELISA KIT. | Blood samples collected before and after 2 hours at lunch on the no-breakfast day; blood samples collected before and after 2 hours at next day breakfast on the no-dinner day | 
| Results of continuous glucose monitoring | Continuous glucose will be monitored by Abott glucose monitor. | From the day before the first intervention day and the wash-out period till the day after the second intervention day (10 days in total) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from fasting to postprandial blood lipids | Fasting and postprandial total-, HDL-, LDL-cholesterol, triglyceride will be tested. | Blood samples collected before and after 2 hours at lunch on the no-breakfast day; blood samples collected before and after 2 hours at next day breakfast on the no-dinner day | 
| Analyzes of clock gene expression in peripheral blood cells (PBC) | Clock gene expression in PBC will be evaluated by RT-PCR. | PBC samples collected before and after 2 hours at lunch on the no-breakfast day; blood samples collected before and after 2 hours at next day breakfast on the no-dinner day | 
| Analyzes of postprandial plasma metabolome | Non-targeted plasma metabolites will be tested by LC-MS-MS after 2 hours of each meal. | Blood samples collected at 2 hours after each meal | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Time-Restricted Fasting, Postprandial Blood Glucose, Continuous Glucose Monitoring, Crossover trial