Gluten SensitivityNCT06884241
Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity.
A study testing Probiotic supplementation in people with Gluten Sensitivity and Wheat Sensitivity, run by University of Turin, Italy at 1 site in Italy.
Trial summary
The aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate the effects of probiotics on symptoms and gut microbiota composition following gluten reintroduction. The study included adults diagnosed with NCWS. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Gluten Sensitivity, Wheat Sensitivity
- What is being tested?
- Probiotic supplementation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteItaly
- Study dates
- 10 Sep 2018to 10 Jan 2025
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age≥18 years
- NCGWS demonstrated by the following self-reported conditions i) intestinal and extra intestinal symptoms associated within hours or days after the ingestion of gluten-containing food, ii) a clear benefit while on a gluten-free diet, iii) relapse of symptoms with the ingestion of gluten-containing foods, iv) a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test, as previously described.
Who cannot join
- presence of Crohn disease (CD), wheat allergy (WA), irritable bowel syndrome (IBS), and other gastrointestinal diseases, H. Pylori infection, lactose intolerance, history of gastrointestinal surgery, liver/pancreatic diseases, active or recent infection diseases, known psychiatric diseases, any systemic diseases
- pregnancy or breastfeeding
- active use of antibiotics, pre-probiotics, immunosuppressive drugs, non-steroidal anti-inflammatory drugs, or corticosteroids,
- inability to give written informed consent.
Trial locations and contacts
1 site in 1 country.
Italy1 site
AOU Città della Salute e della Scienza di Torino, University of Torino
Torino, 10126
About this study
Official title: Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity. A Randomized Controlled Double-blind Trial.
The aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate the effects of probiotics on symptoms and gut microbiota composition following gluten reintroduction.
The study included adults diagnosed with NCWS. Participants received a 6-week intervention with either probiotics or a placebo. For the first 4 weeks, all participants followed a gluten-free, low-FODMAP diet, after which gluten was reintroduced.
Gastrointestinal symptoms (using the modified Gastrointestinal Symptom Rating Scale (GSRS)) and fecal samples were collected at baseline (T0), after 4 weeks (T1), and after 6 weeks (T2). Gut microbiome composition was assessed through whole-shotgun metagenomic sequencing and fecal volatile organic compounds (VOCs) were analyzed using gas chromatography-mass spectrometry (GC-MS).
Read the detailed description
Non-Celiac Gluten Sensitivity (NCGS), or Non-Celiac Wheat Sensitivity (NCWS), is a condition characterized by the onset of gastrointestinal and systemic symptoms following the consumption of gluten-containing foods, without the presence of celiac disease or wheat allergy.
The aim of the present randomized, double-blind controlled trial is to explore probiotics as a potential therapeutic option to alleviate symptoms and improve gut microbiome composition.
Participants Eligible participants were adults aged 18 or older with NCGWS, confirmed by a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test. Those with conditions like Crohn's disease, wheat allergy, IBS, gastrointestinal issues, infections, psychiatric disorders, or those on specific medications, as well as pregnant or breastfeeding individuals, were excluded.
Intervention Participants were randomized to receive for 6 weeks 2 sachets of probiotics (Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106) (experimental arm) or 2 sachets of placebo (control arm). All participants a gluten-free and low FODMAPs diet. After 4 weeks, foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten).
The investigators and the participants were blinded to the procedure. The probiotic and placebo sachets were identical and in identical packaging.
Measurements
At baseline (T0), after 4 weeks (T1, end of gluten-free diet), and after 6 weeks (T2, study-end), participants were submitted to the following measurements:
- modified GSRS questionnaire
- collection of a fecal sample for gut microbiota determination. At T1 and T2, volatile organic fractions of stool samples were assessed and whole shotgun metagenomics were performed.
- Conditions
- Gluten Sensitivity, Wheat Sensitivity
- Being tested
- Probiotic supplementation, Placebo
- Keywords
- gluten sensitivity, wheat sensitivity, probiotics, microbiome
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotic supplementationDietary supplement
The intervention consists of a 6-week supplementation with a specific combination of probiotics: Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106. All participants were given a gluten-free, low FODMAPs diet. After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained
PlaceboOther
The participants received placebo for 6 weeks. Placebo was identical in appearance, texture, taste, and packaging to the probiotic treatment. All participants were given a gluten-free, low FODMAPs diet.
After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Participants in this arm received a supplementation of probiotics for 6 weeks. Receives: Dietary Supplement: Probiotic supplementation |
| Control arm | Placebo comparator | Participants in this arm received placebo for 6 weeks. The placebo were identical in size, shape, color, and taste to the probiotic. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Symptoms Following Gluten Reintroduction
The primary outcome was evaluating between-group differences in symptoms reported by participants after gluten reintroduction, as measured by the modified Gastrointestinal Symptom Rating Scale (GSRS), according to the Salerno Experts criteria. Participants were defined as "tolerant" to the gluten-containing diet if their total GSRS scores did not change or reduced 2 weeks after the gluten introduction (T2)
Measured: Symptoms were assessed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Secondary outcomes (2)
Gut microbiome composition after probiotic supplementation
The assessment of gut microbiome composition after probiotic supplementation. Gut microbiome composition was assessed through whole-shotgun metagenomic sequencing.
Measured: Gut microbiome was analyzed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Fecal volatilome after probiotic supplementation
The assessment of volatilome after probiotic supplementation by gas chromatography-mass spectrometry
Measured: Volatilome was analyzed at baseline and after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2025
- Study start10 Sep 2018
- Primary completion3 Dec 2024
- Study completion10 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gluten SensitivityStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Simona Bo, University of Turin, Italy
- Investigators
- Simona Bo, Associate Professor, MD, Principal investigator, University of TorinoIlario Ferrocino, Professor, Study director, University of Turin, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06884241
- Sponsor's protocol ID
- GLUTEN_2024
- Status last verified
- Mar 2025
- First submitted
- 7 Mar 2025
- Last updated
- 19 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a Probiotic Supplementation on Symptoms and Microbiome Characteristics in Patients With Non-celiac Gluten/Wheat Sensitivity. A Randomized Controlled Double-blind Trial.
- ClinicalTrials.gov ID
- NCT06884241
- Acronym / sponsor ID
- GLUTEN_2024
- Conditions
- Gluten Sensitivity, Wheat Sensitivity
- Keywords
- gluten sensitivity, wheat sensitivity, probiotics, microbiome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 3 Dec 2024 (actual)
- Study completion
- 10 Jan 2025 (actual)
- First posted
- 19 Mar 2025 (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.
The aim of this randomized, double-blind, placebo-controlled clinical trial is to investigate the effects of probiotics on symptoms and gut microbiota composition following gluten reintroduction.
The study included adults diagnosed with NCWS. Participants received a 6-week intervention with either probiotics or a placebo. For the first 4 weeks, all participants followed a gluten-free, low-FODMAP diet, after which gluten was reintroduced.
Gastrointestinal symptoms (using the modified Gastrointestinal Symptom Rating Scale (GSRS)) and fecal samples were collected at baseline (T0), after 4 weeks (T1), and after 6 weeks (T2). Gut microbiome composition was assessed through whole-shotgun metagenomic sequencing and fecal volatile organic compounds (VOCs) were analyzed using gas chromatography-mass spectrometry (GC-MS).
Detailed description
Non-Celiac Gluten Sensitivity (NCGS), or Non-Celiac Wheat Sensitivity (NCWS), is a condition characterized by the onset of gastrointestinal and systemic symptoms following the consumption of gluten-containing foods, without the presence of celiac disease or wheat allergy.
The aim of the present randomized, double-blind controlled trial is to explore probiotics as a potential therapeutic option to alleviate symptoms and improve gut microbiome composition.
Participants Eligible participants were adults aged 18 or older with NCGWS, confirmed by a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test. Those with conditions like Crohn's disease, wheat allergy, IBS, gastrointestinal issues, infections, psychiatric disorders, or those on specific medications, as well as pregnant or breastfeeding individuals, were excluded.
Intervention Participants were randomized to receive for 6 weeks 2 sachets of probiotics (Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106) (experimental arm) or 2 sachets of placebo (control arm). All participants a gluten-free and low FODMAPs diet. After 4 weeks, foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten).
The investigators and the participants were blinded to the procedure. The probiotic and placebo sachets were identical and in identical packaging.
Measurements
At baseline (T0), after 4 weeks (T1, end of gluten-free diet), and after 6 weeks (T2, study-end), participants were submitted to the following measurements:
- modified GSRS questionnaire
- collection of a fecal sample for gut microbiota determination. At T1 and T2, volatile organic fractions of stool samples were assessed and whole shotgun metagenomics were performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Dietary Supplement: Probiotic supplementationParticipants in this arm received a supplementation of probiotics for 6 weeks. |
| Control arm | Placebo comparator | Other: PlaceboParticipants in this arm received placebo for 6 weeks. The placebo were identical in size, shape, color, and taste to the probiotic. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- age≥18 years
- NCGWS demonstrated by the following self-reported conditions i) intestinal and extra intestinal symptoms associated within hours or days after the ingestion of gluten-containing food, ii) a clear benefit while on a gluten-free diet, iii) relapse of symptoms with the ingestion of gluten-containing foods, iv) a positive response to the double-blind placebo-controlled (DBPC) cross-over gluten challenge test, as previously described.
Key exclusion criteria (4 listed)
- presence of Crohn disease (CD), wheat allergy (WA), irritable bowel syndrome (IBS), and other gastrointestinal diseases, H. Pylori infection, lactose intolerance, history of gastrointestinal surgery, liver/pancreatic diseases, active or recent infection diseases, known psychiatric diseases, any systemic diseases
- pregnancy or breastfeeding
- active use of antibiotics, pre-probiotics, immunosuppressive drugs, non-steroidal anti-inflammatory drugs, or corticosteroids,
- inability to give written informed consent.
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 |
|---|---|---|
| Probiotic supplementationThe intervention consists of a 6-week supplementation with a specific combination of probiotics: Lactiplantibacillus plantarum P17630 49x109, Lacticaseibacillus paracasei I1688 1x109, Ligilactobacillus salivarius I1794 25x106. All participants were given a gluten-free, low FODMAPs diet. After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained | Dietary supplement | Intervention arm |
| PlaceboThe participants received placebo for 6 weeks. Placebo was identical in appearance, texture, taste, and packaging to the probiotic treatment. All participants were given a gluten-free, low FODMAPs diet. After 4 weeks (T1), foods containing gluten were reintroduced in the diet of all participants (at least 6 g/day of gluten), while the reduced FODMAP content was maintained | Other | Control arm |
Primary outcome
Change in Symptoms Following Gluten Reintroduction
Time frame: Symptoms were assessed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
The primary outcome was evaluating between-group differences in symptoms reported by participants after gluten reintroduction, as measured by the modified Gastrointestinal Symptom Rating Scale (GSRS), according to the Salerno Experts criteria. Participants were defined as "tolerant" to the gluten-containing diet if their total GSRS scores did not change or reduced 2 weeks after the gluten introduction (T2)
2 secondary outcomes
Gut microbiome composition after probiotic supplementation
Time frame: Gut microbiome was analyzed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
Fecal volatilome after probiotic supplementation
Time frame: Volatilome was analyzed at baseline and after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).
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 19 Mar 2025.
- Individual participant dataSharing planned: No
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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.
Simona Bo, Associate Professor, MD principal investigator
University of Torino
Ilario Ferrocino, Professor study director
University of Turin, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic supplementation in people with Gluten Sensitivity and Wheat Sensitivity, run by University of Turin, Italy at 1 site in Italy.
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 2 inclusion and 4 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 19 Mar 2025. 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 Italy. 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 Symptoms Following Gluten Reintroduction (time frame: Symptoms were assessed at baseline (T0), after 4 weeks of a gluten-free diet (T1), and after 2 weeks of gluten reintroduction (T2).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Mar 2025.