Lactobreath: A Study to Diagnose Lactose Intolerance Using Breath Markers
- Conditions
- Lactose Intolerance
- Interventions
- Dietary Supplement: Lactose solution/Glucose solution
- Registration Number
- NCT06177938
- Lead Sponsor
- ETH Zurich
- Brief Summary
Food intolerances affect many people and can cause discomfort and dietary challenges. One common cause is difficulty digesting certain carbohydrates called FODMAPs. Diagnosing food intolerance is often done by excluding and then slowly reintroducing these carbohydrates or using a hydrogen breath test, but these methods have limitations.
To address these issues, this project uses the breath we exhale to find markers for lactose intolerance as a model for food intolerance diagnosis. Our aim is to identify breath markers for lactose tolerance and intolerance and link them to metabolic traits, including those found in urine. We use a real-time breath analysis method and a special sensor to measure gases in the digestive system, and we also explore genetic factors using saliva samples.
This project aims to help clinicians better identify patients who should follow low FODMAP diets and provide non-invasive breath tests to predict how patients will respond to these diets. It will also advance the use of breath analysis for personalized nutrition, contributes to the broader field of food intolerance research, and has the potential to benefit millions of individuals worldwide.
- Detailed Description
Genetic and lactose tolerance screening For all eligible participants, a screening home test will be conducted. The home screening test kit will contain lactose powder and accompanying information in order for the subjects to conduct a lactose tolerance test (according to the LHBT protocol) at home. The test will be adapted from recent guidelines (https://www.esnm.eu/guidelines.html) that propose the use of 25g of lactose for lactose tolerance testing, including a questionnaire to quantitatively assess symptoms. The home screening test kit will also provide material to collect a saliva sample to determine genetic polymorphisms commonly modulating LP.
A total of 120 participants will be selected and distributed into three groups based on their LP genetic profiles and response to the ingestion of 25 g of lactose (lactose solution):
* 24 genetically LP subjects with no GI symptoms in response to the ingestion of lactose (group 1)
* 24 genetically lactase-non-persistent (LNP) subjects with no GI symptoms in response to the ingestion of lactose (group 2)
* 72 genetically LNP subjects with any GI symptoms in response to lactose ingestion (group 3).
Study procedures Baseline measures: For each subject, baseline measurement of microbiota and diet will be made within four weeks of the intervention day. The assessment of diet and the genomic characterization of the fecal microbiota will be performed in parallel with repeated measures
* Four 24 h dietary recalls will be completed using an adapted version of the myfood24 online platform on four consecutive days, during days -30 to -7, before the intervention day
* Three fecal samples will be collected by the participants at home, ideally on three consecutive days, on days +1, +2, and +3 relative to the first 24 h dietary recall.
Intervention day: The diet of all selected participants will be restricted for the three days before the carbohydrate challenge test day to ensure that all FODMAPs are avoided with a standardized diet provided to the participants for the three days before the test.
On the morning of the test day, the participants will be asked to collect their first test sample, the morning urine and consume 300 mL of water at home. Upon arrival in the test laboratory, the participants will deliver a further urine sample and baseline breath samples for the breath metabolome and hydrogen breath test. The urine samples will be used for metabolomics analysis and, in the case of female participants, for a pregnancy test. Participants with a positive pregnancy test will be excluded.
The participants will also fill out the questionnaire on LI (as used for the screening survey) to describe symptoms of LI before the test (baseline symptoms).
The 120 participants will be assigned to one of the two carbohydrate challenges using stratified randomization based on the three groups defined by the pre-screening tests. 100 participants will be assigned to the experimental intervention (lactose). The remaining 20 participants (4 participants from each groups 1 and 2 and 12 participants from group 3) will be assigned to the control intervention (glucose). The participants and investigators will be blinded during testing to the type of carbohydrate solution assigned.
For each participant, the carbohydrate solution will need to be consumed in a time-lapse of 5 min. Following the solution intake, participants will be asked to rinse their mouths with a standard quantity of water (500 mL) to avoid the detection of solution-relevant residual molecules in the oral cavity. The participants will swallow a commercially available gas-sensing capsule within the 5 minutes following the lactose or glucose solution intake to monitor intestinal gases and GI transit time.
Postprandial breath, exhaled breath condensate (EBC) and urine samples will then be collected at predefined times during the 6 h following consumption of the assigned test product. Breath sampling will be performed using a secondary electrospray ionization source coupled to a high-resolution mass spectrometry system (SESI-HR-MS) for direct and real-time detection of volatile organic compounds (VOC) and using an H2 breath sensor (e.g. QuinTron BreathTracker Digital Microlyzer) for detection of exhaled hydrogen. EBC samples will be collected using a spirometry filter connected to a glass cold trap cooled to -78°C. In addition, the participants will fill out the questionnaire for symptoms of LI to describe the symptoms during the 6 h postprandial assessment .
To normalize participants' hydration, particularly to facilitate the urine collection, the participants will be offered a standardized quantity of water based on their body weight to be consumed in regular portions during the post-ingestion period. No other foods or fluids will be permitted during the laboratory testing.
Intestinal excretion of the gas-sensing capsule will mark the end of the intervention. A follow-up visit to confirm the excretion of the gas-sensing capsule will conclude the study.
Additional subjects will be recruited should the number of participants completing the lactose and glucose tests fall below the targeted numbers.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lactose solution Lactose solution/Glucose solution Single ingestion of a lactose solution (25 g lactose dissolved in 150 mL water). Glucose solution Lactose solution/Glucose solution Single ingestion of a glucose solution (13 g glucose dissolved in 150 mL water).
- Primary Outcome Measures
Name Time Method Diagnostic performance of the breath profile associated with lactose malabsorption (lactobreath profile) Breath samples will be collected at 9 time points following the ingestion of lactose (15 min, 30 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min). Selected metabolites identified from exhaled breath after lactose intake that can collectively discriminate clinical traits associated with lactose malabsorption. Several parameters with be assessed: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio of a positive test (LR+), the likelihood ratio of a negative test (LR-).
- Secondary Outcome Measures
Name Time Method Metabolome of exhaled breath condensate (EBC) samples 9 postprandial timepoints following lactose intake (15 min, 30 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min) Metabolites identified in EBC samples using standardized LC-MS methods (reversed-phase and HILIC) and GC-MS.
Clinical symptoms of lactose intolerance 5 postprandial timepoints following lactose intake (30 min, 60 min, 120 min, 180 min, and 360 min) Standardized questionnaire previously validated for the target population
Urine metabolome Two pooled postprandial timepoints following lactose intake (0-3h and 3-6h) Metabolites identified in urine samples using GC-qTOF (including lactose and its metabolites, galactose, galactitol, and galactonate).
Hydrogen breath test 9 postprandial timepoints following lactose intake (15 min, 30 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min) Dynamic assessment of the hydrogen in breath after dietary exposure using hydrogen breath sensor
Intestinal gases and GI transit assessment Semi-continuous (every 20 seconds) postprandial assessment following lactose intake until excretion of the capsule Dynamic assessment of the environment of the intestine via a commercial gas-sensing capsule to evaluate intestinal gas concentrations (H2, O2, CO2, and CH4), pH and GI transit.
Trial Locations
- Locations (1)
ETH Zurich
🇨🇭Zürich, Zurich, Switzerland