Ignite Creation Date:
2024-05-06 @ 7:41 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06094894
Status:
COMPLETED
Last Update Posted:
2024-03-12
First Post:
2023-10-17
Brief Title:
Effects of Sucralose in Gut Intestinal Microbiota and Postprandial GLP-1
Sponsor:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Organization:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Overview
Official Title:
Changes in Gut Microbiota and Postprandial GLP-1 Concentration Due to Sucralose Consumption
Status:
COMPLETED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Recently it has been proposed that the consumption of non-nutritive sweeteners including sucralose its not harmless and is related with metabolic effects Some studies have reported that sucralose produces alterations in glucose homeostasis In vitro studies indicate that sucralose can interact with sweet taste receptors T1R2 and T1R3 in the intestine thus increasing the expression of glucose transporters including the sodium-glucose cotransporter type 1 SGLT1 and the glucose transporter 2 GLUT2 increasing glucose absorption This interaction with intestinal sweet taste receptors also generates an increase in the secretion of the incretins glucagon-like peptide type 1 GLP-1 and the glucose-dependent insulinotropic polypeptide GIP which might enhance the postprandial insulin release However these results are preliminary and its desirable to confirm if sucralose consumption is associated with glucose metabolism modifications using an appropriate methodological design and with gold standard methods The aim of this triple-blind placebo-controlled parallel randomized clinical trial is to confirm the changes in insulin sensitivity associated with sucralose consumption in humans to identify whether these changes are in the liver or skeletal muscle and to investigate the pathophysiological mechanisms generating these changes Specifically we will investigate if sucralose generates a dysbiosis in the gut microbiota that could be related to insulin resistance by increasing concentrations of lipopolysaccharide a toxin found in Gram-negative bacteria that triggers a low-grade inflammation known as metabolic endotoxemia In addition the changes in postprandial concentrations of GLP-1 glucose insulin and C-peptide due to the combination of sucralose with a mixed meal will be investigated The results of this study will determine if sucralose consumption frequently used as a non-nutritive sweetener is associated to significant changes in glucose homeostasis in humans
Detailed Description:
Study design
This is a triple-blind parallel placebo-controlled randomized clinical trial
Sample size
The sample size was calculated to observe a difference of 25 in GLP-1 area under the curve
The calculation was done considering a probability of type I error α of 5 with a power of 80 and adding an extra 20 for potential losses at follow-up
The estimated sample size for the study is 40 subjects 20 per group
Randomization
The participants will be randomly assigned to one of the two groups sucralose or placebo using the website Randomizationcom httpwwwrandomizationcom with a balanced block design of 5 blocks with 8 subjects each The random allocation sequence will be done by an external researcher
Intervention
The intervention will consist of capsules filled with pure sucralose or placebo cornstarch accordingly to the group assignment Each capsule will contain 90 mg of sucralose or placebo Participants will be asked to consume one capsule in each meal three per day in order to achieve an ingestion of 270 mg of sucralose or placebo this quantity corresponds approximately to the 30 of the acceptable daily intake ADI of sucralose for a lean person This was calculated based on the ADI established by the joint Food and Agriculture Organization of the United Nations FAOWorld Health Organization WHO expert committee on food additives JECFA of 15 mg per kg of body weight per day of sucralose
The use of identical capsules will allow the blinding the capsules will be deposited in bottles numbered sequentially according to the enrollment process and neither the participants nor the researches will know the content of the capsules or the group assigned
Visit 1
An oral glucose tolerance test OGTT will be performed to confirm that participants do not have diabetes or prediabetes Fasting insulin lipid profile and glycated hemoglobin will be measured Also anthropometry weight height waist and hip circumference blood pressure and heart rate will be documented Body composition will be evaluated with dual X-ray absorptiometry DXA already available in the Research Unit and bioelectrical impedance Physical activity will be registered with the questionnaire from the University of Laval that measure energy expenditure in Kcal per day A format for three-day food intake record will be given to be prospectively registered by participants
Visit 2
The three-day food record will be requested and reviewed to evaluate food consumption habits A mixed meal tolerance test will be performed over two hours The meal will consist of 523 kcal 49 carbohydrates 17 protein 34 lipids Blood samples will be collected at 0 30 60 90 and 120 minutes to measure glucose insulin and glucagon-like peptide type 1 GLP-1 concentrations Also lipopolysaccharide LPS C-reactive protein CRP interleukin 6 IL-6 and tumor necrosis factor-alpha TNF-α concentrations will be measured at the basal time Ten minutes before the test participants will consume a capsule containing either sucralose or placebo 120 mg
Participants will proportionate the first stool sample to evaluate gut microbiota
The researchers will proportionate the bottle with capsules that each participant will consume during the intervention period 30 2 days in this visit Also each participant will be asked to record on the adherence format if they consumed the capsule at breakfast lunch and dinner each day of the intervention period and to record any symptom related to capsules ingestion Another format to record three-day food consumption again will be given
Visit 3
Participants will proportionate the second stool sample to evaluate changes in gut microbiota Also the physical activity questionnaire will be applied again and the second 3-day food record will be obtained to evaluate changes in physical activity and food habits respectively The second mixed meal tolerance test will be performed following the same procedures as visit 2 Participants will be asked to return the empty bottles to quantify adherence to the intervention In addition adherence and symptoms formats will be collected
Visit 4
Participants will be asked to assist one month after visit 3 to make a final evaluation of fasting glucose insulin and lipid profile concentrations The physical activity questionnaire will be applied again and a third 3-day food record will be collected to evaluate changes in physical activity and food habits respectively
This is a triple-blind parallel placebo-controlled randomized clinical trial
Sample size
The sample size was calculated to observe a difference of 25 in GLP-1 area under the curve
The calculation was done considering a probability of type I error α of 5 with a power of 80 and adding an extra 20 for potential losses at follow-up
The estimated sample size for the study is 40 subjects 20 per group
Randomization
The participants will be randomly assigned to one of the two groups sucralose or placebo using the website Randomizationcom httpwwwrandomizationcom with a balanced block design of 5 blocks with 8 subjects each The random allocation sequence will be done by an external researcher
Intervention
The intervention will consist of capsules filled with pure sucralose or placebo cornstarch accordingly to the group assignment Each capsule will contain 90 mg of sucralose or placebo Participants will be asked to consume one capsule in each meal three per day in order to achieve an ingestion of 270 mg of sucralose or placebo this quantity corresponds approximately to the 30 of the acceptable daily intake ADI of sucralose for a lean person This was calculated based on the ADI established by the joint Food and Agriculture Organization of the United Nations FAOWorld Health Organization WHO expert committee on food additives JECFA of 15 mg per kg of body weight per day of sucralose
The use of identical capsules will allow the blinding the capsules will be deposited in bottles numbered sequentially according to the enrollment process and neither the participants nor the researches will know the content of the capsules or the group assigned
Visit 1
An oral glucose tolerance test OGTT will be performed to confirm that participants do not have diabetes or prediabetes Fasting insulin lipid profile and glycated hemoglobin will be measured Also anthropometry weight height waist and hip circumference blood pressure and heart rate will be documented Body composition will be evaluated with dual X-ray absorptiometry DXA already available in the Research Unit and bioelectrical impedance Physical activity will be registered with the questionnaire from the University of Laval that measure energy expenditure in Kcal per day A format for three-day food intake record will be given to be prospectively registered by participants
Visit 2
The three-day food record will be requested and reviewed to evaluate food consumption habits A mixed meal tolerance test will be performed over two hours The meal will consist of 523 kcal 49 carbohydrates 17 protein 34 lipids Blood samples will be collected at 0 30 60 90 and 120 minutes to measure glucose insulin and glucagon-like peptide type 1 GLP-1 concentrations Also lipopolysaccharide LPS C-reactive protein CRP interleukin 6 IL-6 and tumor necrosis factor-alpha TNF-α concentrations will be measured at the basal time Ten minutes before the test participants will consume a capsule containing either sucralose or placebo 120 mg
Participants will proportionate the first stool sample to evaluate gut microbiota
The researchers will proportionate the bottle with capsules that each participant will consume during the intervention period 30 2 days in this visit Also each participant will be asked to record on the adherence format if they consumed the capsule at breakfast lunch and dinner each day of the intervention period and to record any symptom related to capsules ingestion Another format to record three-day food consumption again will be given
Visit 3
Participants will proportionate the second stool sample to evaluate changes in gut microbiota Also the physical activity questionnaire will be applied again and the second 3-day food record will be obtained to evaluate changes in physical activity and food habits respectively The second mixed meal tolerance test will be performed following the same procedures as visit 2 Participants will be asked to return the empty bottles to quantify adherence to the intervention In addition adherence and symptoms formats will be collected
Visit 4
Participants will be asked to assist one month after visit 3 to make a final evaluation of fasting glucose insulin and lipid profile concentrations The physical activity questionnaire will be applied again and a third 3-day food record will be collected to evaluate changes in physical activity and food habits respectively
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None