NCT07183254

Resting-state Imaging and Chronic Consumption of Non-Nutritive SweetenerS

Resting-state Functional Imaging in Chronic Consumption of Non-energetic Artificial Sweeteners

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: University Hospital, Clermont-Ferrand · Academic / Other
• Sex: All
• Age: 18 Years – 30 Years
• Healthy volunteers: Accepted

Summary

Non-nutritive sweeteners are used as a substitute for simple sugars to improve the palatability of food products without increasing their sugar and calorie content. They represent a global market of 7 billion euros, with an annual growth of 5%. Reducing their consumption therefore seems to be excluded. Some studies have focused on the impacts of these substances on brain activity. According to a recent study, continuous consumption of low doses of saccharin in adult mice significantly decreases the level of dopamine in the prefrontal cortex and significantly increases striatal dopamine, which modifies decision-making strategies. Resting-state functional Magnetic Resonance Imaging (r-fMRI) studies in humans have also shown that an increase in striatal dopaminergic activity modifies the resting-state functional connectivity of brain regions linked to the reward circuit. r-fMRI allows the characterization of brain networks and the strength of correlations between brain regions, without any specific task being required. It is a rapid, non-invasive technique that can measure changes in brain functional connectivity. In addition to r-fMRI, diffusion tensor imaging (DTI) is able to assess white matter microstructure and the integrity or otherwise of fiber tracts. Several parameters such as the fractional anisotropy (FA), coefficient of white matter, mean diffusivity, and radial diffusivity can be modified in the event of changes in functional connectivity, reflecting axonal rearrangements, not visible on conventional MRI sequences. Based on previous research, investigators hypothesize that (1) chronic consumption of non-nutritive artificial sweeteners increases striatal dopaminergic activity. (2) This modification is accompanied by changes in resting-state functional connectivity in brain regions of interest associated with the reward circuit in healthy young adults. Then, the primary objective of this study is to compare, in the resting state, the differences in functional connectivity of brain regions of interest between "non/low consumers" and "high consumers" of sweeteners at the start of the study using r-fMRI. The key secondary objective of this study is to assess changes in brain connectivity using r-fMRI in non- and low-consuming subjects before and after a transient increase in their sweetener consumption over 5 weeks. The secondary objectives include assessing daily sugar consumption (5-week follow-up), daily consumption of non-energy-rich artificial sweeteners (5-week follow-up), Body Mass Index (BMI), physical activity level, and white matter microstructure and fibrous tract integrity using a diffusion-weighted MRI (DTI) sequence.

Detailed description

A single-center interventional study in 35 non- and low-consumers (approximately 8 mg/day) and 35 high-consumers (approximately 70 mg/day) selected, among other things, using a quantitative consumption frequency questionnaire on daily sugar and sweetener intake, whose frequency scale has been validated by a previous study. The subjects recruited are healthy young adults, aged 18 to 30 years. An initial f-rMRI and DTI session will be performed for both groups (non- and low-consumers and high-consumers of sweeteners). Then, a second session will be conducted after 5 weeks of nutritional intervention only in non- and low-consumers of sweeteners. During this period, subjects will be asked to consume 660 ml of sweetened carbonated beverages, the equivalent of 2 cans per day, with or without meals. They will also be asked to record their daily sugar and sweetener consumption, using an adapted version of the previously mentioned consumption frequency questionnaire, during this same period. The study will observe initial differences in brain connectivity between non- and low-consumers and high-consumers of sweeteners, as well as changes in connectivity in non- and low-consumers before and after the nutritional intervention. Comparison of functional connectivity between non- and low consumers and high consumers, as well as the change in connectivity before and after nutritional intervention in non- and low consumers will be performed by comparing connectivity matrices among all possible pairs of regions of interest, with a t-test for independent samples (between non- and low consumers and high consumers at t = 0) and dependent samples (non- and low consumers pre- and post-nutrition intervention; t = 0 and t = 5 weeks). Results will be expressed in terms of effect sizes and 95% confidence intervals. At baseline (t = 0), the assessment of daily intake of simple sugars and BMI, as well as the level of physical activity, will be analyzed in relation to the consumption of non-nutritive artificial sweeteners, using a one-way ANOVA or a Kruskal-Wallis test, and a Chi-square test or a Fisher's exact test, respectively. The assessment of intakes of simple sugars and non-nutritive artificial sweeteners during the 5 weeks of nutritional intervention (t = 5 weeks) in non- and low-consumers will be compared to the intakes of sugars and sweeteners estimated at t = 0, using a dependent-samples t-test or a Mann-Whitney test, if the conditions for applying the t-test are not met. The results will be expressed in terms of effect size and 95% confidence interval. To describe changes in white matter microstructure in non- and low-drinkers compared with high-drinkers, anisotropic fraction and ADC will be compared by Student's t-test or Mann-Whitney test. Results will be expressed as effect sizes and 95% confidence intervals.

Conditions

• Healthy Volunteers - Male and Female

Interventions

Type	Name	Description
OTHER	administration of questionnaires	During this visit, the investigator will again explain the study objectives and procedure. Once these explanations have been provided, healthy volunteers will be able to give their informed consent to participate. After signing the consent form, the following will be conducted during this visit: * A medical examination. * An electronic questionnaire including two consumption frequency assessment tools, adapted in French, to measure daily sugar and artificial sweetener intake. * Five tests assess the level of dependence on alcohol, drugs (cannabis, solvents, tranquilizers, barbiturates, cocaine, stimulants, hallucinogens, or narcotics), gambling, video games, and possible eating disorders. Volunteers with a score deemed above the norm for at least one of these six tests will be excluded from this study. * A urine screening test for drug use (cannabis, opiates, amphetamines, cannabinoids, benzodiazepines, cocaine) will be performed during this visit.
OTHER	carrying out a MRI scan	A functional exploration using resting-state fMRI and microstructural tissue organization using DTI will take place in the days following the inclusion visit, depending on the availability of "research" slots in the Department of Radiology and Imaging, Clermont-Ferrand University Hospital.
DIETARY_SUPPLEMENT	Can distribution visit for subjects in the "non/low" sweetener consumption group	During this visit, scheduled following the MRI, subjects will go to the PIC/CIC where they will be given cans for the 5 weeks of the nutritional intervention (660 ml of sweetened beverage, or 2 cans per day). Subjects will be advised to arrive by car if possible and to park in the PIC/CIC parking lot at the foot of the building. Drinks will be provided to the subject in one or two batches (with an additional visit to the center to pick up any missing drinks) at the subject's convenience. They will also receive instructions for completing the electronic questionnaire to assess daily sugar and sweetener consumption. Subjects will complete this questionnaire weekly, which they will receive by email. Their email address will be collected during this visit.
OTHER	carrying out a MRI scan	A functional exploration using resting-state fMRI and microstructural tissue organization using DTI, post-nutritional intervention (5 weeks) in non- and low-sugar consumers: this exploration will take place depending on the availability of "research" slots at the Department of Radiology and Imaging, Clermont-Ferrand University Hospital.

Timeline

• Start date: 2025-10-01
• Primary completion: 2026-12-01
• Completion: 2027-12-01
• First posted: 2025-09-19
• Last updated: 2025-09-19

Locations

1 site across 1 country: France