Evaluation of Methods for Measuring Gastrointestinal Transit and Food Reward in Healthy Individuals - The PRESET Study

Study Overview
=================
Brief Summary
-----------------
The wireless motility capsule technology, SmartPill™, can be used to assess gastric emptying and gastrointestinal (GI) transit time. The SmartPill is usually ingested together with a SmartBar™ which is a snack bar with a nutrient composition that differs substantially from a normal western diet. The primary aim of the present study is to compare effects of a SmartBar™ and a standard mixed meal on gastric emptying and GI motility.

Detailed Description
-----------------
Background: The wireless motility capsule technology, SmartPill™, can be used to assess GI transit time including gastric emptying and small and large bowel transit time based on measurements of pH, pressure and temperature. The SmartPill™ allows for GI motility measurements under free-living conditions without radiation. The SmartPill is usually ingested together with a SmartBar™ which is a snack bar with a nutrient composition that differs substantially from a normal western diet. GI motility in response to meals plays an important role in regulation of e.g. appetite and glucose metabolism. Changes in appetite and metabolism in response to interventions are often assessed using a meal test and GI motility is assessed at the research facilities. The use of SmartPill™ in combination with a meal test would allow for assessment of GI motility under subsequent free-living conditions and improve our understanding of the effects of interventions on the integrative relationship between food intake, GI motility and metabolism. Most of our daily decisions and actions affecting energy intake are driven by the non-conscious processes; however, appetite is often assessed from participants' self-report which is associated with limitations such as desire to report socially desirable answers. Little is known about the complex interrelationship between biological markers of appetite e.g. GI hormones and subjective and objective measures of food related behavior under fasting and fed conditions. The PRESET study has the following objectives: To compare effects of a SmartBar™ and a standard mixed breakfast meal on gastric emptying and GI transit time measured using the SmartPill™ in normal-weight individuals. To compare effects of a SmartBar™ and a standard mixed breakfast meal on concentrations of metabolites and pancreatic and GI hormones, and subjective and objective measures of appetite, food reward and food related behavior assessed from biometric responses (facial expression, galvanic skin response and eye tracking) to visual food stimuli varying in fat content and taste during the computerized Leeds Food Preference Questionnaire (LFPQ) in normal-weight individuals. To assess potential associations between gastric emptying and GI motility, biological markers of appetite and subjective appetite and objective measures of food related behavior from biometric responses to visual food stimuli during the LFPQ in the fasting state and in response to meals in normal-weight individuals. Testing includes assessments in the fasting state and in response to consumption of the SmartBar™ and a standard mixed meal (4-hour meal tests and subsequent 6-days free-living assessment period) on two separate test days.

Official Title
-----------------
Evaluation of Methods for Measuring Gastrointestinal Transit and Food Reward in Healthy Individuals - The PRESET Study

Conditions
-----------------
Healthy Participants

Intervention / Treatment
-----------------
* Other: Standard mixed breakfast meal
* Other: SmartBar™


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Body mass index: 18.5 to 24.9 kg/m2 Exclusion Criteria: Unable to understand the informed consent and the study procedures; Self-reported history of an eating disorder in the past three years Self-reported weight change (>5 kg) within three months prior to inclusion HbA1c: ≥5.7 % (≥39 mmol/mol) Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, GI or psychiatric disease; diabetes or other endocrine disease; immunosuppression Current treatment with medication or medical devices which affect GI motility and transit time (prokinetics, antidiarrheals, laxatives) Current treatment with medication which affect glucose metabolism or appetite Current treatment with beta blockers or peroral steroids Current treatment with non-steroidal anti-inflammatory drugs, tricyclic antidepressants, selective serotonin re-uptake inhibitors or opioids Bariatric surgery GI symptoms or diseases such as regular (weekly) abdominal pain, dysphagia, gastric bezoars, strictures, fistulas, bowel obstructions, diverticulitis, celiac disease, Crohn's disease, ulcerative colitis or proctitis Alcohol/drug abuse or in treatment with disulfiram (Antabus) at time of inclusion Pregnant or lactating women Fertile women not using birth control agents including oral contraceptives, gestagen injection, subdermal implants, hormonal vaginal ring, transdermal application, or intra-uterine devices Concomitant participation in other research studies

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The study is a randomized cross-over study including 15 healthy normal-weight individuals. On two separate test days participants ingest the SmartPill™ in combination with a SmartBar™ (standard procedure, reference) or a standard mixed breakfast meal.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SmartBar™<br>The wireless capsule technology, SmartPill™, is usually ingested together with a SmartBar™ which is a snack bar with a nutrient composition that differs substantially from a normal western diet. | Other: SmartBar™<br>* SmarBar™ (Medtronic, North Haven, MA, USA). Weight: 72 g; Total energy content: 260 kcal Macronutrient composition: 7 E% fat, 19 E% protein, 74 E% carbohydrate.<br>|
| Experimental: Standard mixed breakfast meal<br>The SmartPill™ is ingested together with a standard mixed breakfast meal and the outcomes of interest will be compared with the SmartBar™ condition (reference). | Other: Standard mixed breakfast meal<br>* The standard mixed breakfast meal consists of: 150 g yoghurt, 20 g muesli; 50 g wheat bun; 22 g rye bread; 25 g cheese; 25 g marmalade; 8 g butter; Total energy content: 500 kcal Macronutrient composition: 34 E% fat, 17 E% protein, 49 E% carbohydrate<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastric emptying time (minutes) | Measured by the SmartPill™ technique. The SmartPill™ is ingested at both visits in combination with the standard breakfast meal and SmartBar™, respectively. The time frame depends on the individual gastric emptying time. | Within 24 hours from ingestion of the SmartPill™ at both visits (standard breakfast meal and SmartBar™, respectively) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Small bowel transit time (minutes) | Measured by the SmartPill™ technique. The SmartPill™ is ingested at both visits in combination with the standard breakfast meal and SmartBar™, respectively. The time frame depends on the individual transit time. | Within 5 days after both visits (standard breakfast meal and SmartBar™, respectively) | 
| Large bowel transit time (minutes) | Measured by the SmartPill™ technique. The SmartPill™ is ingested at both visits in combination with the standard breakfast meal and SmartBar™, respectively. The time frame depends on the individual transit time. | Within 5 days after both visits (standard breakfast meal and SmartBar™, respectively) | 
| Total gastrointestinal transit time (minutes) | Measured by the SmartPill™ technique. The SmartPill™ is ingested at both visits in combination with the standard breakfast meal and SmartBar™, respectively. The time frame depends on the individual transit time. | Within 5 days after both visits (standard breakfast meal and SmartBar™, respectively) | 
| Motility index (arbitrary unit) | Calculated based on amplitudes and number of contractions measured using the SmartPill™ technique. The greater the motility index the greater the gastrointestinal motility (i.e. more frequent and stronger contractions). A higher motility index has been observed among healthy participants compared to patients with diabetic gastroparesis indicating that a higher index is favorable. | Within 5 days after both visits (standard breakfast meal and SmartBar™, respectively) | 
| Metabolites | Concentrations of metabolites (including but not limited to: glucose, lipids, cholesterol, free-fatty acids, and amino acids. Measured at both visits in the fasting state and for 4 hours after consumption of the standard breakfast meal and the SmartBar™, respectively. | 0 minutes (fasting) and 15, 30, 45, 60, 90, 120, 180, 240 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Hormones | Concentrations of hormones related to regulation of appetite, glucose and lipid metabolism (including but not limited to: insulin, glucagon, ghrelin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and peptide YY (PYY), leptin, fibroblast growth factor 19 (FGF-19), fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF-15)). | 0 minutes (fasting) and 15, 30, 45, 60, 90, 120, 180, 240 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Attention measured using eye tracking | Eye tracking metrics including gaze duration bias, gaze direction bias, fixations, saccades, pupil size/dilation, distance to screen, ocular vergence and blinks to measure attention in response to looking at food pictures during the computerized Leeds Food Preference Questionnaire | 0 minutes (fasting) at 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Arousal measured using galvanic skin response | Changes in conductivity of skin (galvanic skin response) in response to looking at food pictures during the computerized Leeds Food Preference Questionnaire | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Emotions measured using facial expression analysis | Facial expression analyses using computer-vision algorithms (AFFDEX) to measure emotions in response to looking at food pictures during the computerized Leeds Food Preference Questionnaire | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Food choice | Food choice of food items from four combined food categories (high-fat savoury, high-fat sweet, low-fat savoury and low-fat sweet foods) examined from the computerized Leeds Food Preference Questionnaire. Food choice is determined based on frequency of selection made within each food category. The scores range from 0-48 i.e. 0 = foods within a specific food category have not been selected at all to 48 = foods within a specific food category have been selected 48 times. | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Implicit wanting | Implicit wanting of food items from four combined food categories (high-fat savoury, high-fat sweet, low-fat savoury and low-fat sweet foods) examined from the computerized Leeds Food Preference Questionnaire. Implicit wanting is assessed based on food choice and response time for selected and non-selected food items as well as mean response time. | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Explicit liking | Explicit liking of 16 food items from four combined food categories (high-fat savoury, high-fat sweet, low-fat savoury and low-fat sweet foods) examined from the computerized Leeds Food Preference Questionnaire. Explicit liking is rated using visual analogue scales and the range is 0-100. Each end represents the extremes e.g. Question: how pleasant would it be to taste this food right now? Answer: not at all (rated 0 on the 0-100 scale) to extremely (rated 100 on the 0-100 scale). | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Explicit wanting | Explicit wanting of 16 food items from four combined food categories (high-fat savoury, high-fat sweet, low-fat savoury and low-fat sweet foods) examined from the computerized Leeds Food Preference Questionnaire. Explicit wanting is rated using visual analogue scales and the range is 0-100. Each end represents the extremes e.g. Question: how much do you want some of this food now? Answer: not at all (rated 0 on the 0-100 scale) to extremely (rated 100 on the 0-100 scale). | 0 minutes (fasting) and after 60 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Subjective appetite | Rated using visual analogue scales and includes sensations of: Hunger, fullness, satiety, prospective food consumption, wellbeing, nausea, thirst, desire to eat meat, salty, and sweet. The scale range is 0-100 and each end represent the extremes e.g. hunger rating: I am not hungry at all to I have never been this hungry before. | 0 minutes (fasting) and 15, 30, 45, 60, 90, 120, 180, 240 minutes (after consumption of the standard breakfast meal and SmartBar™, respectively) | 
| Self-reported gastrointestinal symptoms (part 1) | Assessed from the questionnaire the Gastrointestinal Symptom Rating Scale (GSRS). Rated on 7-point likert scales. Range: 1 = absence of symptoms to 7 = very severe symptoms. | Answered during test days (0-240 minutes) | 
| Self-reported gastrointestinal symptoms (part 2) | Assessed from the Gastrointestinal Symptom Score (PAGI-SYM). Rated on 6-point likert scales. Range: 1 = absence of symptoms to 6 = very severe symptoms. | Answered during test days (0-240 minutes) | 
| Self-reported gastrointestinal symptoms (part 3) | Number of symptoms. Assessed from logs. | Registered 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Self-reported autonomic symptoms | Assessed from the questionnaire COMPASS31 | Answered during test days (0-240 minutes) | 
| Body weight (kg) | Body weight is measured on a digital scale | At 0 minutes (fasting) at both visits | 
| Body mass index (kg/m^2) | Calculated from body weight (kg) and height (m) | At 0 minutes (fasting) at both visits | 
| Fat mass (kg) | Measured by Dual-energy X-ray Absorptiometry | At 0 minutes (fasting) at both visits | 
| Fat percentage (%) | Measured by Dual-energy X-ray Absorptiometry | At 0 minutes (fasting) at both visits | 
| Fat free mass (kg) | Measured by Dual-energy X-ray Absorptiometry | At 0 minutes (fasting) at both visits | 
| Waist circumference (cm) | Measured using tape measure | At 0 minutes (fasting) at both visits | 
| Hip circumference (cm) | Measured using tape measure | At 0 minutes (fasting) at both visits | 
| Mean amplitude of glycaemic excursions (MAGE) | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Continuous overall net glycaemic action (CONGA) | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Daily time spent above different glucose concentrations (e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L) | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Mean glucose concentrations | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Standard deviation of glucose concentrations | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Variation coefficients of glucose concentrations | Measured using continous glucose monitoring | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Resting energy expenditure (kcal/day) | Measured by indirect calorimetry under resting and fasting conditions | At 0 minutes (fasting) at both visits | 
| Substrate oxidation (respiratory exchange ratio) | Measured by indirect calorimetry under resting and fasting conditions | At 0 minutes (fasting) at both visits | 
| Systolic blood pressure (mmHg) | Measured under resting and fasting conditions | At 0 minutes (fasting) at both visits | 
| Diastolic blood pressure (mmHg) | Measured under resting and fasting conditions | At 0 minutes (fasting) at both visits | 
| Heart rate (bpm) | Measured under resting and fasting conditions during measurements of blood pressure and in the supine position by a handheld ECG measuring device (Vagus™). | At 0 minutes (fasting) at both visits | 
| Heart rate response to standing up from the supine position | Measured by a handheld ECG measuring device (Vagus™). | At 0 minutes (fasting) at both visits | 
| Heart rate response to inhalation and exhalation | Measured by a handheld ECG measuring device (Vagus™). | At 0 minutes (fasting) at both visits | 
| Heart rate response to forced exhalation during rest (valsalva maneuver) | Measured by a handheld ECG measuring device (Vagus™). | At 0 minutes (fasting) at both visits | 
| Microbiome content and diversity | Determined from stool samples. Bacterial DNA and RNA will be purified from the stool samples and changes in the microbiome composition and function will be estimated based on sequencing of the microbiomes' DNA and RNA. Includes but is not limited to the Firmicutes/Bacteroidetes ratio. | One sample during 6 days after both visits | 
| Physical activity (time spent at different intensities) | Sedentary time, light, moderate and vigorous intensity physical activity. Assessed from 24 h/day accelerometry | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Physical activity (counts/min) | Assessed from 24 h/day accelerometry | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Physical activity energy expenditure (kcal/day) | Assessed from 24 h/day accelerometry | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Physical activity (MET hours) | Assessed from 24 h/day accelerometry | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Timing of physical activity (hh:mm) | Assessed from activity logs and 24 h/day accelerometry | Measured for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Energy intake (kcal/day) | Assessed from diet records | Assessed for 3 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Macronutrient intake (energy percentage) | Assessed from diet records | Assessed for 3 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Timing of dietary intake (hh:mm) | Assessed from diet records | Assessed for 3 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Sleep timing (hh:mm) | Including bedtime, sleep onset, wake-up, time out of bed, sleep midpoint. Assessed from sleep logs and 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Sleep duration (minutes) | Assessed from sleep logs and 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Sleep variability (minutes) | Variability in bedtime, wake-up, sleep duration and sleep midpoint. Assessed from sleep logs and 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Sleep onset latency (minutes) | Assessed from sleep logs and 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Sleep efficiency (%) | Assessed from 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| Wakefulness (minutes) | Assessed from 24 h/day accelerometry | Assessed for 6 days after both visits (standard breakfast meal and the SmartBar™ conditions) | 
| HbA1c (mmol/mol and %) | Hemoglobin A1c | At 0 minutes at both visits | 
| Insulin sensitivity (indices) | Including but not limited to the Matsuda index | At 0 minutes (fasting) and 4 hours after consumption of the standard breakfast meal and the SmartBar™, respectively | 
| Insulin resistance (indices) | Including but not limited to Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) | At 0 minutes (fasting) and 4 hours after consumption of the standard breakfast meal and the SmartBar™, respectively | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastric emptying, Gastrointestinal transit, Food reward, Food preferences