SENSILINS: Impact of Cephalic Phase Insulin Release Induced by an Environmental Food Odor Stimulus on Glucose Homeostasis According to Insulin Sensitivity Level (SENSILNS)

Impact of Cephalic Phase Insulin Release Induced by an Environmental Food Odor Stimulus on Glucose Homeostasis According to Insulin Sensitivity Level

This single-center, randomized, single-blind, 2-period crossover interventional study will evaluate whether exposure to a pleasant food odor 10 minutes before a 75 g oral glucose tolerance test (OGTT) modifies glucose homeostasis in adults with different metabolic phenotypes. Participants will undergo two experimental conditions in random order: food odor stimulation and control condition without odor, separated by a 4-week washout. The main objective is to quantify the within-subject effect of food odor stimulation on the incremental area under the glucose curve (iAUC) from 0 to 120 minutes during OGTT and to assess whether this effect differs according to metabolic status. Two predefined groups will be enrolled: adults without overweight and without insulin resistance, and adults with class I obesity and low-to-moderate insulin resistance. Secondary objectives include characterization of cephalic phase insulin release (CPIR), C-peptide and GLP-1 responses, glycemic kinetics, associations between CPIR and metabolic responses, and participant acceptability of the test environment and olfactory stimulation. A plasma biobank will be constituted from part of the collected samples for future research.

Study Overview

• Status: Not yet recruiting
• Conditions: Insulin Resistance Syndrome; Obesity & Overweight
• Intervention / Treatment: Behavioral: Pleasant Food Odor Stimulation; Behavioral: Control Environmental Condition

Detailed Description

Recent experimental and translational data suggest that olfactory cues may contribute to metabolic regulation through anticipatory cephalic phase responses. Cephalic phase insulin release (CPIR) is an early preabsorptive insulin response triggered by sensory food-related stimuli before nutrient absorption. Preclinical data generated by the study team suggest that food-odor-induced CPIR involves an olfactory bulb-pancreas axis and may be altered in obesity. The present study is designed to investigate, in humans, whether a pleasant appetitive food odor delivered before glucose ingestion can induce measurable CPIR and improve post-load glucose handling.

The study uses a randomized AB/BA crossover design with two experimental visits after screening and inclusion. During one visit, participants are exposed to prerecorded food odor diffusion using a ScentRealm collar starting at T-10 minutes before ingestion of a 75 g glucose solution at T0. During the control visit, the same testing environment is maintained without odor stimulation. Serial blood sampling is performed before and after glucose ingestion to characterize glucose, insulin, C-peptide, and GLP-1 kinetics. The washout period is 4 weeks (±3 days), partly to align visits within the same menstrual cycle phase in women when applicable. The trial includes 20 adults aged 18 to 50 years: 10 without overweight and insulin-sensitive, and 10 with obesity and low-to-moderate insulin resistance defined using HOMA-IR.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne Laure MD CASTELL, Dr; Phone Number: +33 +33 4 78 86 19 72; Email: anne-laure.castell@chu-lyon.fr

Study Locations

• France
  • Pierre-Bénite, France, 69495
    • Centre de Recherche en Nutrition Humaine Rhône-Alpes, Centre Hospitalier Lyon Sud
    • Contact: Anne Laure CASTELL, MD; Phone Number: +33 +33 4 78 86 19 72; Email: anne-laure.castell@chu-lyon.fr
    • Contact: Nathalie Feugier-Favier, MD; Phone Number: +33 +33 4 78 86 29 54; Email: nathalie.feugier@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Age 18 to 50 years inclusive
• Stable body weight during the previous 3 months (±5% of total body weight)
• Willing to comply with the full study protocol
• Sedentary lifestyle or stable regular physical activity, with agreement to keep this unchanged throughout the study
• Able to understand study information, read and write French, and provide written informed consent
• Affiliated with a social security scheme or equivalent
• Non-smoker and non-vaper
• Willing not to take dietary supplements, probiotics, prebiotics, or laxatives for 10 days before each visit
• For women of childbearing potential: negative serum pregnancy test; not pregnant and not breastfeeding
• Mean score between 1 and 2 on the 3 specific CiTAS questionnaire statements used as inclusion criteria
• ETOC flash olfactory screening: able to detect the odor-containing vial among 4 presented vials for all 7 odors tested
• Able to identify the madeleine odor used in the study
• Rated pleasantness/appetence of the madeleine odor above 1/9
• For the no-overweight group: BMI 19 to <25 kg/m² and HOMA-IR <1.7
• For the obesity group: BMI 30 to <35 kg/m² and low-to-moderate insulin resistance based on HOMA-IR [protocol inconsistency to resolve; see note below]

Exclusion Criteria

• Unstable medical or psychological conditions that could impair compliance, safety, or study participation in the investigator's judgment
• Alcohol consumption >30 g/day, or established abuse/dependence on another drug
• Ongoing exclusion period from another study listed in the national volunteer file
• Legal protection measure (guardianship/curatorship)
• Deprivation of liberty by judicial or administrative decision
• Exceeded annual compensation limit for research participation
• Lack of valid required health documentation in the event of exceptional governmental epidemic measures
• Blood donation within 2 months before inclusion visit
• Limited venous access making repeated blood sampling/catheter placement difficult
• Current or permanent anosmia or olfactory disorder
• Type 1 or type 2 diabetes, treated or untreated
• History of gestational diabetes
• Known or treated hypertension
• Blood pressure >160 [unit missing; likely mmHg systolic threshold]
• Dyslipidemia, treated or untreated
• Triglycerides >3 mmol/L
• Allergic rhinitis
• Nasosinusal polyposis
• History of intestinal or abdominal surgery except appendectomy or simple hernia repair
• History of ENT or neurological surgery
• Severe eating disorder (for example anorexia, bulimia, binge-eating disorder, night eating)
• Any pathology detected on clinical examination or medical interview judged by the investigator to interfere with study endpoints or participant safety
• Any biological abnormality judged by the investigator to interfere with study endpoints or participant safety
• Use of treatments likely to interfere with study measurements, for example antidepressants, antiepileptics, neuroleptics, CPAP treatment for sleep apnea, nasal spray medications, or anti-obesity drug treatment, according to investigator judgment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Food Odor Stimulation; Participants are exposed to a pleasant appetitive food odor delivered through a ScentRealm collar beginning 10 minutes before ingestion of a 75 g oral glucose load and continuing according to a prerecorded sequence during the metabolic test visit.	Behavioral: Pleasant Food Odor Stimulation; Exposure to an experimentally selected appetitive food odor (madeleine odor) delivered using a programmable ScentRealm collar in a standardized test room beginning at T-10 minutes before OGTT.; Behavioral: Control Environmental Condition; Standardized testing environment identical to the experimental visit but without diffusion of the appetitive food odor.
Placebo Comparator: Control Condition; Participants undergo the same standardized metabolic test visit and OGTT procedures in the same test environment without food odor stimulation.	Behavioral: Pleasant Food Odor Stimulation; Exposure to an experimentally selected appetitive food odor (madeleine odor) delivered using a programmable ScentRealm collar in a standardized test room beginning at T-10 minutes before OGTT.; Behavioral: Control Environmental Condition; Standardized testing environment identical to the experimental visit but without diffusion of the appetitive food odor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-subject difference in glucose incremental area under the curve (iAUC) from 0 to 120 minutes during OGTT	Primary endpoint is the mean within-subject difference between food odor and control conditions in glucose incremental area under the curve from 0 to 120 minutes after oral glucose ingestion. Glucose iAUC will be calculated using the trapezoidal method, baseline-adjusted to glucose at T0. The main analysis will also assess the interaction between condition (odor vs control) and metabolic status (no overweight/insulin-sensitive vs obesity with low-to-moderate insulin resistance). Unit should be specified in the statistical analysis plan according to assay reporting (for example mmol/L×min or mg/dL×min).	During each experimental visit, from 0 to 120 minutes after ingestion of the 75 g oral glucose load

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preabsorptive and early post-ingestion insulin iAUC as a measure of cephalic phase insulin release	Incremental area under the curve for insulin during the pre-ingestion and early post-ingestion period (0 to 15 minutes), compared by condition and metabolic status. Additional CPIR-related metrics include latency, peak concentration, slope, and percentage of responders. Unit to specify according to assay output (for example µIU/mL×min or pmol/L×min).	From pre-OGTT odor exposure through 15 minutes after glucose ingestion during each experimental visit
Preabsorptive and early post-ingestion C-peptide iAUC	Incremental area under the curve for C-peptide during the pre-ingestion and early post-ingestion period (0 to 15 minutes), compared by condition and metabolic status. Additional metrics include latency, peak concentration, slope, and percentage of responders. Unit to specify according to assay output.	From pre-OGTT odor exposure through 15 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - Δmax	Effect of condition and metabolic status on glycemic maximum change from baseline (Δmax)	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - Time to peak	Effect of condition and metabolic status on the necessary amount of time to reach glycemic peak in minutes	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - Growth curve slope	Effect of condition and metabolic status on the slope of the glycemic growth curve from baseline	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - Decay curve slope	Effect of condition and metabolic status on the slope of the glycemic decay curve from the maximum (peak)	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - ultradian oscillation indices	Effect of condition and metabolic status on ultradian oscillation indices	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - iAUC (0 to 120 min)	Effect of condition and metabolic status on Incremental Area Under the Curve (IAUC) from 0 to 120 min for glucose	From 0 to 120 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - early glucose iAUC (0-30min)	Effect of condition and metabolic status on glucose Incremental Area Under the Curve (IAUC) from 0 to 30 min	From 0 to 30 minutes after glucose ingestion during each experimental visit
Glycemic kinetic response during OGTT - late glucose iAUC (30-120 min)	Effect of condition and metabolic status on glucose Incremental Area Under the Curve (IAUC) from 30 to 120 min	From 30 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - iAUC (0-120 min)	Total Incremental Area Under the Curve (iAUC) from 0 to 120 minutes	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - iAUC (0-30min)	Insulin Incremental Area Under the Curve (IAUC) from 0 to 30 min	From 0 to 30 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - iAUC (30-120min)	Insulin Incremental Area Under the Curve (IAUC) from 30 to 120 min	From 30 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - Δmax	The value of the maximum (peak) of the curve relative to the baseline value for insulin	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - Time to peak	Necessary amount of time for insulin to reach peak in minutes	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - Growth curve slope	Slope of the insulin growth curve from baseline	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for insulin during OGTT - Decay curve slope	Slope of the insulin decay curve from the maximum (peak)	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - iAUC (0-120min)	C-peptide Incremental Area Under the Curve (IAUC) from 0 to 120 min	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - iAUC (0-30min)	C-peptide Incremental Area Under the Curve (IAUC) from 0 to 30 min	From 0 to 30 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - iAUC (30-120min)	C-peptide Incremental Area Under the Curve (IAUC) from 30 to 120 min	From 30 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - Δmax	The value of the maximum (peak) of the curve relative to the baseline value for C-peptide	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - Time to peak	Necessary amount of time for C-peptide to reach peak in minutes	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - Growth curve slope	Slope of the C-peptide growth curve from baseline	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for C-peptide during OGTT - Decay curve slope	Slope of the C-peptide decay curve from the maximum (peak)	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - iAUC (0-120min)	GLP1 Incremental Area Under the Curve (IAUC) from 0 to 120 min	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - iAUC (0-30min)	GLP-1 Incremental Area Under the Curve (IAUC) from 0 to 30 min	From 0 to 30 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - iAUC (30-120min)	GLP-1 Incremental Area Under the Curve (IAUC) from 30 to 120 min	From 30 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - Δmax	The value of the maximum (peak) of the curve relative to the baseline value for GLP-1	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - Time to peak	Necessary amount of time for GLP-1 to reach peak in minutes	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - Growth curve slope	Slope of the GLP-1 growth curve from baseline	From 0 to 120 minutes after glucose ingestion during each experimental visit
Hormonal response parameters for GLP-1 during OGTT - Decay curve slope	Slope of the GLP-1 decay curve from the maximum (peak)	From 0 to 120 minutes after glucose ingestion during each experimental visit
Correlation between CPIR characteristics and metabolic/hormonal responses	Correlations between CPIR features and subsequent glucose response during OGTT (including glucose iAUC 0-120 and early/late components) and hormonal quantitative/kinetic responses, including assessment of interaction with metabolic status.	Assessed using measurements collected during each experimental visit up to 120 minutes after glucose ingestion
Participant-rated appreciation of the experimental odor	Appreciation of the experimental odor and related emotions assessed using Likert scales at the end of the odor visit, with comparison by condition and metabolic status where applicable. Exact scale range and anchor wording are not provided in the available protocol text.	Week 2 ; Week 4
Participant-rated acceptability of the test environment - Temperature	Acceptability and appreciation of the temperature of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires.	Week 2 ; Week 4
Participant-rated acceptability of the test environment - Lighting	Acceptability and appreciation of the lighting of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires.	Week 2 ; Week 4
Participant-rated acceptability of the test environment - Sound	Acceptability and appreciation of the sound of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires.	Week 2 ; Week 4
Participant-rated acceptability of the test environment - Odor	Acceptability and appreciation of the odor of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires.	Week 2 ; Week 4

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; Glucose Homeostasis; Oral glucose tolerance test; Insulin secretion; Olfaction; Cephalic Phase Insulin Release; Food odor
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Sensation Disorders; Insulin Resistance; Hyperinsulinism; Olfaction Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Anosmia; Overweight; Obesity; Metabolic Syndrome
• Other Study ID Numbers: 69HCL25_1107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: No IPD sharing statement is provided in the available protocol for the moment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No