Irritable Bowel SyndromeFODMAPsNCT04283487
Brain and Gut Responses to Intragastric Administration of FODMAPs in Healthy Subjects and Patients With Irritable Bowel Syndrome
A study testing Fructans, Glucose and Saline in people with Irritable Bowel Syndrome, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Low fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) diet is taken as a possible strategy to improve symptoms in IBS patients. However, the gut-brain signalling mechanisms underlying this observation remain poorly understood. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Irritable Bowel Syndrome
- What is being tested?
- Fructans, Glucose and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteBelgium
- Study dates
- 22 Feb 2018to 10 Aug 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- No symptoms or history of gastrointestinal disease or disorder, other significant diseases
- Female
- Age 18 - 55 years
- Body Mass Index (BMI) of 19 - 28 kg/m2
- Stable body weight for at least 3 months prior to the start of the study
- Right-handed or ambi-dexter
Show all 13Show fewer
- Meet the Rome IV criteria for irritable bowel syndrome (IBS)
- Patient has IBS of any subtype
- Female
- Age 18 - 55 years
- Body Mass Index (BMI) of 19 - 28 kg/m2
- Stable body weight for at least 3 months prior to the start of the study
- Right-handed or ambi-dexter
Who cannot join
- Medical
- Abdominal or thoracic surgery. Exception: appendectomy
- Gastrointestinal, endocrine or neurological diseases
- Cardiovascular, respiratory, renal or urinary diseases
- Hypertension
- Food or drug allergies
Show all 39Show fewer
- Anemia Psychiatric disorders
- Eating disorders
- Depressive disorders
- Anxiety disorders
- Psychotic disorders Medication use
- No regular medication affecting CNS or GI system (oral contraception accepted) Other
- Conditions that can interfere with functional magnetic resonance imaging (fMRI), e.g. cochlear implants, metal fragments or metal implants in the body, pacemaker, neural stimulator, …
- No history of cannabis use or any other drug of abuse for at least 12 months prior to the study
- Alcohol abuse (more than 14 units for woman per week)
- People who show abnormal eating behavior or have followed a gluten-free or low-FODMAP diet previously
- Pregnant or breastfeeding women
- Claustrophobia
- IBS patients:
- General exclusion criteria for all subjects:
- Medical
- Abdominal or thoracic surgery. Exception: appendectomy
- Gastrointestinal, endocrine or neurological diseases
- Cardiovascular, respiratory, renal or urinary diseases
- Hypertension
- Food or drug allergies
- Anemia Psychiatric disorders
- Eating disorders
- Depressive disorders
- Anxiety disorders
- Psychotic disorders Medication use
- No regular medication affecting CNS or GI system (oral contraception accepted)
- Other
- Conditions that can interfere with functional magnetic resonance imaging (fMRI), e.g. cochlear implants, metal fragments or metal implants in the body, pacemaker, neural stimulator, …
- No history of cannabis use or any other drug of abuse for at least 12 months prior to the study
- Alcohol abuse (more than 14 units of alcohol per week)
- People who show abnormal eating behavior, or have followed a gluten-free or low-FODMAP diet previously
- Pregnant or breastfeeding women
- Claustrophobia
Trial locations and contacts
1 site in 1 country.
About this study
Low fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) diet is taken as a possible strategy to improve symptoms in IBS patients. However, the gut-brain signalling mechanisms underlying this observation remain poorly understood. In this study, the investigators aim to study the brain mechanisms underlying the effect of intragastric administration of one specific FODMAP (fructans) on gastrointestinal and non- gastrointestinal symptom responses, changes in gut physiology(morphology of the gut, water content and intestinal motility), and to relate the findings to changes in gastrointestinal peptides. Intragastric administration of three different solutions will be given after an overnight fast: one FODMAP solution (fructans), a positive control (glucose) and a negative control (saline). The whole procedure consists of a functional magnetic resonance imaging (fMRI) and abdominal MRI examination, and will take approximately four hours. The participants will undergo the fMRI for one hour for assessing brain activity, during which blood samples will be collected. The abdominal MRI will be performed at 1-hour interval for three hours to assess pre and post stimulated changes in gut physiology, specifically the morphology of the gut water content and pan-intestinal motility. During the whole procedure, questionnaires for assessing the gastrointestinal symptoms and emotional state will be collected. The investigators hypothesise that fructans induce distension and increased sensations of pain, cramps and flatulence in the IBS group more than the HC. Furthermore, this will be associated with increased activation of pain-responsive brain regions in IBS compared to HC, which will be mediated by differential changes in gut peptide levels (↓ in orexigenic and ↑ in anorexigenic hormones).
Read the detailed description
In this study, the investigators aim to study the brain mechanisms underlying the effect of intragastric administration of one specific FODMAP (fructans) on gastrointestinal and non- gastrointestinal symptom responses, changes in gut physiology(morphology of the gut, water content and intestinal motility), and to relate the findings to changes in gastrointestinal peptides.
This is a randomised, double-blinded, crossover study. Eligible participants will come three times to the clinic after an overnight fast, for intragastric infusion of fructans (40g in 500 ml water), glucose(40g in 500ml water) or saline(0.9% 500ml normal saline). The infusions will be given in counterbalanced order and with a washout period of at least one week. Participants and investigators will be blinded to the nature of the test solution, which will be made by a colleague unrelated to the study. The order of the test solutions will be determined by a computer-generated list. All participants will be asked to follow the low FODMAP diet for the 24 hours prior to each study day. Participants will be asked to record their food intake during the day to check their FODMAP intakes were reduced.
To begin, the participants will have a nasogastric feeding tube placed and an intravenous cannula inserted in the non-dominant arm to facilitate repeated blood sampling. Fifteen minutes later, they will enter the MR scanner for a 5 minute adaptation period. Participants will complete visual analogue scales (VAS) on appetite-related sensations and GI symptoms and blood samples will be collected for gut peptide analysis. Current emotional state will be rated before and after scanning using the PANAS, and during scanning using the POMS. The abdominal MRI scan will begin after the adaption period and will take 10 minutes. Hereafter, brain scanning will be performed, starting with a baseline brain scanning period of 10 minutes. After the baseline scanning, 500 mL of one of the three solutions will be infused as the functional brain imaging begins (and continues for 50 minutes). The VAS ratings will be collected every 10 minutes and blood samples will be collected every 20 minutes for measuring of ghrelin, CCK, GLP-1, motilin, and PYY, insulin and glucose throughout the scan. At 60 minutes post-infusion, a 10 minute abdominal scan will be acquired. After that, the subject leaves the scanner and the catheter will be removed. The subject will remain at the facility for a 2 hour follow-up during which the VAS ratings will be collected every 30 minutes and an abdominal MRI will be performed at 120 minutes post infusion. After the last abdominal MRI scan is performed, the infusion tube will be removed and the participant can go home.
- Conditions
- Irritable Bowel Syndrome
- Being tested
- Fructans, Glucose, Saline
- Keywords
- FODMAP, Irritable bowel syndrome, brain-gut axis, fMRI, abdominal MR
- Medical subject headings
- Irritable Bowel Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FructansDietary supplement
500ml 0.9% normal saline containing 40g fructans
GlucoseDietary supplement
500ml 0.9% normal saline containing 40g glucose
SalineDietary supplement
500ml 0.9% normal saline
| Study group | Role | What they receive |
|---|---|---|
| Fructans solution | Experimental | Fructans (FODMAP) are oligosaccharides containing fructose chains. Since the human body lacks hydrolases to break down these saccharides, fructans are poorly absorbed molecules in everybody.The fructans solution used in this study is 500 ml water containing 40g fructans Receives: Dietary Supplement: Fructans |
| Glucose solution | Active comparator | Glucose is a carbohydrate that is not classified as FODMAP, and is therefore used as a positive control in this study. The glucose solution used in this study is 500 ml water containing 40g glucose. Receives: Dietary Supplement: Glucose |
| Saline solution | Placebo comparator | The saline solution does't contain any sugar and used in this study is 500ml 0.9% normal saline. Receives: Dietary Supplement: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in brain activation patterns measured by fMRI
change in blood oxygenation level dependent (BOLD) signal by fMRI
Measured: -10 min to 50 min
Secondary outcomes (11)
Change in gastrointestinal symptom scores measured by VAS
bloating, nausea, cramps, flatulence and abdominal pain
Measured: -30 min to 180 min
Change in state emotion score measured by validated questionnaire
emotion score measured by POMS
Measured: -30 min to 180 min
Change in state emotion score measured by validated questionnaire
emotion score measured by PANAS
Measured: -30 min to 180 min
Change in plasma levels of gut peptides
Plasma levels of ghrelin
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of CCK
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of GLP-1
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of motilin
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of PYY
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of insulin
Measured: -20 min to 60 min
Change in plasma levels of gut peptides
Plasma levels of glucose
Measured: -20 min to 60 min
Change in gut physiology measured by abdominal MRI
Gastric emptying and accommodation, antral and small bowel motility, water and gas content measured by abdominal MRI
Measured: -20 min to 180 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2020
- Study start22 Feb 2018
- Primary completion10 Aug 2019
- Study completion10 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomised, double-blind, placebo-controlled, crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jan Tack, MD, PHD, Principal investigator, UZ Leuven / KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04283487
- Sponsor's protocol ID
- FODMAP2
- Acronym
- FODMAPs
- Status last verified
- May 2021
- First submitted
- 21 Feb 2020
- Last updated
- 28 May 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Deidentified individual participant data that underlie the reported results will be made available 3 months after publication for a period of 5 years after the publication date upon request.
Publications
Wu J, Masuy I, Biesiekierski JR, Fitzke HE, Parikh C, Schofield L, Shaikh H, Bhagwanani A, Aziz Q, Taylor SA, Tack J, Van Oudenhove L. Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome. Aliment Pharmacol Ther. 2022 Mar;55(6):670-682. doi: 10.1111/apt.16812. Epub 2022 Feb 15.
PubMed 35166384
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain and Gut Responses to Intragastric Administration of FODMAPs in Healthy Subjects and Patients With Irritable Bowel Syndrome
- ClinicalTrials.gov ID
- NCT04283487
- Acronym / sponsor ID
- FODMAPs / FODMAP2
- Conditions
- Irritable Bowel Syndrome
- Keywords
- FODMAP, Irritable bowel syndrome, brain-gut axis, fMRI, abdominal MR
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 22 Feb 2018 (actual)
- Primary completion
- 10 Aug 2019 (actual)
- Study completion
- 10 Aug 2019 (actual)
- First posted
- 25 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Low fermentable oligo-, di- and monosaccharides and polyols (FODMAPs) diet is taken as a possible strategy to improve symptoms in IBS patients. However, the gut-brain signalling mechanisms underlying this observation remain poorly understood. In this study, the investigators aim to study the brain mechanisms underlying the effect of intragastric administration of one specific FODMAP (fructans) on gastrointestinal and non- gastrointestinal symptom responses, changes in gut physiology(morphology of the gut, water content and intestinal motility), and to relate the findings to changes in gastrointestinal peptides. Intragastric administration of three different solutions will be given after an overnight fast: one FODMAP solution (fructans), a positive control (glucose) and a negative control (saline). The whole procedure consists of a functional magnetic resonance imaging (fMRI) and abdominal MRI examination, and will take approximately four hours. The participants will undergo the fMRI for one hour for assessing brain activity, during which blood samples will be collected. The abdominal MRI will be performed at 1-hour interval for three hours to assess pre and post stimulated changes in gut physiology, specifically the morphology of the gut water content and pan-intestinal motility. During the whole procedure, questionnaires for assessing the gastrointestinal symptoms and emotional state will be collected. The investigators hypothesise that fructans induce distension and increased sensations of pain, cramps and flatulence in the IBS group more than the HC. Furthermore, this will be associated with increased activation of pain-responsive brain regions in IBS compared to HC, which will be mediated by differential changes in gut peptide levels (↓ in orexigenic and ↑ in anorexigenic hormones).
Detailed description
In this study, the investigators aim to study the brain mechanisms underlying the effect of intragastric administration of one specific FODMAP (fructans) on gastrointestinal and non- gastrointestinal symptom responses, changes in gut physiology(morphology of the gut, water content and intestinal motility), and to relate the findings to changes in gastrointestinal peptides.
This is a randomised, double-blinded, crossover study. Eligible participants will come three times to the clinic after an overnight fast, for intragastric infusion of fructans (40g in 500 ml water), glucose(40g in 500ml water) or saline(0.9% 500ml normal saline). The infusions will be given in counterbalanced order and with a washout period of at least one week. Participants and investigators will be blinded to the nature of the test solution, which will be made by a colleague unrelated to the study. The order of the test solutions will be determined by a computer-generated list. All participants will be asked to follow the low FODMAP diet for the 24 hours prior to each study day. Participants will be asked to record their food intake during the day to check their FODMAP intakes were reduced.
To begin, the participants will have a nasogastric feeding tube placed and an intravenous cannula inserted in the non-dominant arm to facilitate repeated blood sampling. Fifteen minutes later, they will enter the MR scanner for a 5 minute adaptation period. Participants will complete visual analogue scales (VAS) on appetite-related sensations and GI symptoms and blood samples will be collected for gut peptide analysis. Current emotional state will be rated before and after scanning using the PANAS, and during scanning using the POMS. The abdominal MRI scan will begin after the adaption period and will take 10 minutes. Hereafter, brain scanning will be performed, starting with a baseline brain scanning period of 10 minutes. After the baseline scanning, 500 mL of one of the three solutions will be infused as the functional brain imaging begins (and continues for 50 minutes). The VAS ratings will be collected every 10 minutes and blood samples will be collected every 20 minutes for measuring of ghrelin, CCK, GLP-1, motilin, and PYY, insulin and glucose throughout the scan. At 60 minutes post-infusion, a 10 minute abdominal scan will be acquired. After that, the subject leaves the scanner and the catheter will be removed. The subject will remain at the facility for a 2 hour follow-up during which the VAS ratings will be collected every 30 minutes and an abdominal MRI will be performed at 120 minutes post infusion. After the last abdominal MRI scan is performed, the infusion tube will be removed and the participant can go home.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Randomised, double-blind, placebo-controlled, crossover
| Arm | Type | Receives |
|---|---|---|
| Fructans solution | Experimental | Dietary Supplement: FructansFructans (FODMAP) are oligosaccharides containing fructose chains. Since the human body lacks hydrolases to break down these saccharides, fructans are poorly absorbed molecules in everybody.The fructans solution used in this study is 500 ml water containing 40g fructans |
| Glucose solution | Active comparator | Dietary Supplement: GlucoseGlucose is a carbohydrate that is not classified as FODMAP, and is therefore used as a positive control in this study. The glucose solution used in this study is 500 ml water containing 40g glucose. |
| Saline solution | Placebo comparator | Dietary Supplement: SalineThe saline solution does't contain any sugar and used in this study is 500ml 0.9% normal saline. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- No symptoms or history of gastrointestinal disease or disorder, other significant diseases
- Female
- Age 18 - 55 years
- Body Mass Index (BMI) of 19 - 28 kg/m2
- Stable body weight for at least 3 months prior to the start of the study
Key exclusion criteria (39 listed)
- Medical
- Abdominal or thoracic surgery. Exception: appendectomy
- Gastrointestinal, endocrine or neurological diseases
- Cardiovascular, respiratory, renal or urinary diseases
- Hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fructans500ml 0.9% normal saline containing 40g fructans | Dietary supplement | Fructans solution |
| Glucose500ml 0.9% normal saline containing 40g glucose | Dietary supplement | Glucose solution |
| Saline500ml 0.9% normal saline | Dietary supplement | Saline solution |
Primary outcome
Change in brain activation patterns measured by fMRI
Time frame: -10 min to 50 min
change in blood oxygenation level dependent (BOLD) signal by fMRI
11 secondary outcomes
Change in gastrointestinal symptom scores measured by VAS
Time frame: -30 min to 180 min
Change in state emotion score measured by validated questionnaire
Time frame: -30 min to 180 min
Change in state emotion score measured by validated questionnaire
Time frame: -30 min to 180 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in plasma levels of gut peptides
Time frame: -20 min to 60 min
Change in gut physiology measured by abdominal MRI
Time frame: -20 min to 180 min
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
- Derived from this study: PubMed 35166384Wu J, Masuy I, Biesiekierski JR, Fitzke HE, Parikh C, Schofield L, Shaikh H, Bhagwanani A, Aziz Q, Taylor SA, Tack J, Van Oudenhove L. Gut-brain axis dysfunction underlies FODMAP-induced symptom generation in irritable bowel syndrome. Aliment Pharmacol Ther. 2022 Mar;55(6):670-682. doi: 10.1111/apt.16812. Epub 2022 Feb 15.
- Individual participant dataSharing planned: Yes. Deidentified individual participant data that underlie the reported results will be made available 3 months after publication for a period of 5 years after the publication date upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jan Tack, MD, PHD principal investigator
UZ Leuven / KU Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Fructans, Glucose and Saline in people with Irritable Bowel Syndrome, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in brain activation patterns measured by fMRI (time frame: -10 min to 50 min). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04283487, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2021.