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

NCT07183254 | Not Yet Recruiting

• 1 other identifier: RBHP 2025 PICKERING
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers - Male and Female

Keywords

non-nutritive sweeteners; non- and low consumers; high consumers; resting-state MRI; diffusion tensor imaging (DTI); reward circuit; resting-state functional connectivity

Outcome Measures

Primary Outcomes (1)

• 1. At rest, functional connectivity between brain areas in healthy subjects, non/low consumers and high consumers of sweetener

  Resting-state functional magnetic resonance imaging (rs-fMRI) is a method that studies the connectivity of different regions of the nervous system. Based on the acquisition of the BOLD (Bond Oxygen Level Dependent) signal, this method focuses more specifically on the study of low-frequency fluctuations (\<0.1 Hz) of this signal. The goal of resting-state imaging is to identify the synchronous activation of different regions of the brain and brainstem, in the absence of a stimulus or a task being performed. This activation can be observed between physically connected regions, or not, and demonstrates the involvement of these regions in a common network called the "Resting State Network" (RSN), which brings together different brain regions involved in common functions; this is referred to as "functional connectivity" between these regions. Areas of interest involved in the reward circuit (amygdala, nucleus accumbens, anterior insula, striatum, the prefrontal cortex, hypothalamus).

  High sweetner consumers: within 4 weeks after enrollment. Low or no sweetner consumer: within 4 weeks after enrollment and immediately after completion of the 5-weeks nutritional intervention.

Secondary Outcomes (8)

• Functional connectivity, at rest, before and after nutritional intervention in non- and low-sugar consumers (criterion for the key secondary objective).

  Immediately after completion of the 5-weeks nutritional intervention.

• The amount of sugar consumed per day during the 5 weeks of nutritional intervention in non- and low-sugar consumers (mg/day).

  Daily during the 5 weeks of the nutritional intervention among non-users and low consumers of sweeteners.

• The amount of artificial sweeteners consumed per day during the 5 weeks of nutritional intervention in non- and low-sugar consumers. (mg/day).

  Daily during the 5 weeks of nutritional intervention in non- and low-sugar consumers.

• Body Mass Index (BMI)

  At enrollment

• Level of physical activity (number of hours of exercise per week).

  At enrollment

Study Arms (2)

Subjects with low or no sweetener consumption, with a gender ratio close to 50/50

EXPERIMENTAL

Subjects will be included: * Men and women aged 18 to 30 (and in good health) * Having low or no sweetener consumption (\~8 mg ± 5.05 mg/day) * Having a BMI of 18.5 \< 24.9 * For young women: having effective contraception maintained throughout the study * Able to give informed consent to participate in the research * Affiliation to a Social Security scheme

Other: administration of questionnaires; Other: carrying out a MRI scan; Dietary Supplement: Can distribution visit for subjects in the "non/low" sweetener consumption group

Subjects with high sweetener consumption, with a gender ratio close to 50/50

EXPERIMENTAL

Subjects will be included: * Men and women aged 18 to 30 (and in good health) * Having high sweetener consumption (\~80 mg ± 91.72 mg/day) * Having a BMI of 18.5 \< 24.9 * For young women: having effective contraception maintained throughout the study * Able to give informed consent to participate in the research * Affiliation to a Social Security scheme

Other: administration of questionnaires; Other: carrying out a MRI scan

Interventions

administration of questionnaires OTHER

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.

Also known as: Visit 1

Subjects with high sweetener consumption, with a gender ratio close to 50/50; Subjects with low or no sweetener consumption, with a gender ratio close to 50/50

carrying out a MRI scan OTHER

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.

Also known as: Visit 2 - Resting-state fMRI and DTI - Department of Radiology and Imaging

Subjects with high sweetener consumption, with a gender ratio close to 50/50; Subjects with low or no sweetener consumption, with a gender ratio close to 50/50

Can distribution visit for subjects in the "non/low" sweetener consumption group DIETARY_SUPPLEMENT

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.

Also known as: Visit 3

Subjects with low or no sweetener consumption, with a gender ratio close to 50/50

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women aged 18 to 30 (and in good health)
• Having low or no sweetener consumption (\~8 mg ± 5.05 mg/day) or high consumption (\~80 mg ± 91.72 mg/day)
• Having a BMI of 18.5 \< 24.9
• For young women: having effective contraception maintained throughout the study
• Able to give informed consent to participate in the research
• Affiliation to a Social Security scheme

You may not qualify if:

• Refusing to participate in the research
• With impaired understanding, according to the investigator
• Volunteer under guardianship/curatorship/deprived of liberty or under legal protection
• Incompatibility of healthy volunteers with the medical imaging center's safety criteria for conducting 3 Tesla MRI experiments
• Presenting "contraindications" to an MRI examination without injection: presence of metal parts in the body (electronic devices such as a pacemaker, a neurostimulator, cochlear implant, prostheses, intraocular foreign bodies, etc.), claustrophobia, obesity
• Refusal to be informed in the event of an incidental discovery of an abnormality on MRI
• Volunteer with neurological disease, psychiatric or behavioral disorders\*
• Volunteer with addiction\*:
• Nicotine: smoker or former smoker of less than 12 months;
• Alcoholism - "AUDIT" test: Female score ≥ 6 and male score ≥ 7;
• Drugs - "DAST-10": Score ≥ 1;
• Gambling - "ICJE": Score ≥ 3
• Video games - Modified DSM IV Video Game Addiction Test: More than 4 positive responses. - Positive urine drug screen
• Volunteer with an eating disorder (ED)\*:
• o Eating disorder - "SCOFF": At least two positive responses. - Volunteers with at least one chronic condition (obesity, diabetes, cardiovascular, renal, or hepatic diseases, etc.)\*

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63000, France

Location

MeSH Terms

Interventions

X-Rays

Intervention Hierarchy (Ancestors)

Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Gisèle Pickering

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

+334.73.754.963; promo_interne_drci@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two Groups: * Healthy subjects, both low and non-sweetener consumers (\~ 8 mg ± 5,05 mg / day), will have to consume 660 ml of sweetened beverage (2 cans) per day, which corresponds to an estimate of more than 87 mg of a mixture of acesulfame K and aspartame, for 5 weeks. * Healthy subjects, high sweetener consumers (\~80 mg ± 91,72 mg / day)

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: September 19, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)