Olfactory Odour Stimulation for Metabolism Control

Study Overview
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Brief Summary
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In this preliminary short-term study it is investigated, whether a short olfactory stimulation with D-Limonene leads to an acute improvement of glucose metabolism in patients with obesity.

Official Title
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Olfactory Odour Stimulation for Metabolism Control - the OLFAMET-Study

Conditions
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Obesity

Intervention / Treatment
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* Other: D-Limonene
* Other: SLVO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years Obesity (BMI ≥35 kg/m2) Written informed consent Normosmia (defined by sniffin Sticks test) Exclusion Criteria: Known allergy to D-Limonene, citrus fruits, citrus flavours, SLVO Regular smoking Current illicit drug abuse including daily marijuana and cannabidiol (CBD) consumption (alcohol ≤2 drinks per day allowed) Diabetes mellitus Pre-Treatment with insulin sensitizing drugs including GLP-1 analogues History of neurodegenerative diseases, severe head trauma Severe renal impairment (e.g. estimated glomerular filtration rate <30 ml/min/m2) Known liver cirrhosis or other severe liver impairment Acute upper respiratory tract infection Uncontrolled dysthyroidism Uncontrolled hypertension Regular use of psychopharmaceutic drugs Patient aims to start a new diet or exercise program during the study Bariatric surgery Pregnancy/Lactation Symptoms of menopause Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. Participation in an interventional study within the last 3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental1<br>During the Cross-Over study, patients will be randomly assigned to one of the arms: Treatment sequence: Placebo at the baseline visit, olfactory Stimulation with D-Limonene at visit 2 and olfactory Stimulation with lavender oil (SLVO) at visit 3 | Other: D-Limonene<br>* Patient will put the aspUraclip®, a commercially available mini-inhalator filled for our study purpose filled with 1% D-Limonene in the nose for 15 minutes<br>Other: SLVO<br>* Patient will put the aspUraclip®, a commercially available mini-inhalator filled for our study purpose filled with 1% SLVO in the nose for 15 minutes<br>|
| Active Comparator: Experimental2<br>During the Cross-Over study, patients will be randomly assigned to one of the arms: Treatment sequence: Placebo at the baseline visit, olfactory Stimulation with SLVO at visit 2 and olfactory Stimulation with D-Limonene at visit 3 | Other: D-Limonene<br>* Patient will put the aspUraclip®, a commercially available mini-inhalator filled for our study purpose filled with 1% D-Limonene in the nose for 15 minutes<br>Other: SLVO<br>* Patient will put the aspUraclip®, a commercially available mini-inhalator filled for our study purpose filled with 1% SLVO in the nose for 15 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of area under blood glucose curve (AUBGC) | area under the blood glucose curve (AUBGC) during a mixed-meal test after stimulation with D-Limonene compared to baseline | Time Frame: baseline blood exam (timepoint 0) and further blood collections: 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUBGC | AUBGC during a mixed-meal test after stimulation with SLVO compared to baseline | Time Frame: baseline blood exam (timepoint 0) and further blood collections: 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Visual Analogue Scale (VAS score) | VAS scores on hunger, appetite, nausea, mood, and hedonics of odour and/or taste of the mixed-meal shake, where 0 equals none, and 10 the maximum of each category | Time Frame: baseline VAS score (timepoint 0) and VAS scores will be evaluated after 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma insulin levels | Plasma insulin levels (mIU/L) | Time Frame: baseline blood exam (timepoint 0) and further blood collections: 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma peak glucose levels | Plasma peak glucose levels (mmol/L) | Time Frame: baseline blood exam (timepoint 0) and further blood collections: 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of glucagon-like peptide 1 (GLP-1) | Plasma levels of GLP-1 (pmol/L) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of gastric inhibitory polypeptide (GIP) | Plasma levels of GIP (pmol/L) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of Ghrelin | Plasma levels of Ghrelin (pg/ml) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of Leptin | Plasma levels of Leptin (ng/ml) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of Peptide YY (PYY) | Plasma levels of PYY (pg/ml) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of Glucagon | Plasma levels of Glucagon (pmol/L) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma Levels of Interleukin-6 | Plasma Levels of Interleukin-6 (pg/ml) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma Levels of C-reactive protein | Plasma Levels of C-reactive protein (μg/ml) | Time Frame: baseline blood exam (timepoint 0) and further blood collections after 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in plasma levels of lipids like LDL-cholesterine, total cholesterine, triglycerides | Plasma levels of lipids (mmol/L) like LDL-cholesterine, total cholesterine, triglycerides | Time Frame: baseline blood exam (timepoint 0) and further blood collections: 5, 15, 30, 60, 90 and 120 minutes after drinking a standardized mixed-meal solution | 
| Change in heart rate | Heart rate (heart beats per minute) | Blood pressure and heart rate will be measured at the following times: baseline (timepoint 0) and 30, 60, 120 minutes drinking a standardized mixed-meal solution | 
| Change in blood pressure | blood pressure (mm Hg) | Blood pressure and heart rate will be measured at the following times: baseline (timepoint 0) and 30, 60, 120 minutes drinking a standardized mixed-meal solution | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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D-limonene, lavender oil (SLVO), Olfactory stimulation, Obesity, glucose metabolism