Gluten SensitivityPhase 3GSNCT01485341
Gluten Sensitivity in Non-Celiac Patients
A Phase 3 study testing gluten and rice starch in people with Gluten Sensitivity, run by University of Campania Luigi Vanvitelli at 7 sites in 2 countries.
Trial summary
The idea is to evaluate if the so called "Gluten Sensitivity" is a real clinical entity. Gluten sensitive (GS) persons are defined as those patients, being neither celiac or allergic to weat, who develop symptoms following gluten consumption. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Gluten Sensitivity
- What is being tested?
- gluten and rice starch
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Jun 2011to Apr 2016
- Phase
- Phase 3
- 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
- Adult patients with age between 18-65 with signs/symptoms compatible with gluten-triggered disorders
- Patients testing negative for celiac disease either by biopsy Marsh 0-1 or those who are HLA-DQ2 and DQ8 negative, as well as tTG and EMA negative
- Patients that improved on a gluten free diet
Who cannot join
- Subjects diagnosed with celiac disease (positive TTG and/or EMA, and histology positive with Marsh II or above);
- Subjects diagnosed with wheat allergy
- Subjects with Type 1 Diabetes (T1D)
- Subjects with Inflammatory Bowel Disease (ulcerative colitis or Crohn's disease)
- Pregnancy
- Subjects with Helicobacter Pylori infection and other gastrointestinal infection
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
Italy6 sites
Università Politecnica delle Marche
Ancona
Gastroenterologia ed Endoscopia digestiva, Ospedale San Giuseppe Moscati
Avellino
Gastroenterology, Second University of Naples
Naples, 80138
Internal Medicine, Policlinico di Palermo
Palermo
Gastroenterology, University of Salerno
Salerno
Ospedale "Casa Sollievo della Sofferenza" - IRCCS -
San Giovanni Rotondo (Foggia)
United States1 site
Center for Celiac Research & Treatment, Yawkey Center for Outpatients Care
Boston, Massachusetts, 02114
About this study
Official title: Double Blind Randomized Placebo Controlled Multicenter Trial (Gluten vs Placebo) in Gluten Sensitive Subjects
The idea is to evaluate if the so called "Gluten Sensitivity" is a real clinical entity. Gluten sensitive (GS) persons are defined as those patients, being neither celiac or allergic to weat, who develop symptoms following gluten consumption. This will be achieved by evaluating a global symptom score in GS patients receiving gluten compared to those receiving placebo (primary end point). Symptoms to be evaluated: gastrointestinal (Gastrointestinal Symptom Rating Scale, GSRS); not-gastrointestinal (specifically built evaluation scale); VQV scale, built to evaluate quality of life. Gluten or placebo will be administered daily (10 g) for 15 days; for the 15 days before and 15 after all patients will stay on Gluten Free Diet (GFD). Besides clinical evaluation (each week for 6 weeks), intestinal permeability testing and blood sampling will be requested for the identification of possible markers (serological, gut barrier function, immunological and expression of tight junctions constitutive proteins) that may be of help to differentiate the condition of gluten sensitivity (GS) from that of Celiac Disease (CD)(secondary end point). Inclusion and exclusion criteria for patients enrolling are strictly dependant on the given "Gluten sensitivity" definition. We expect to experience a worsening of gastrointestinal and extra-gastrointestinal symptoms, from hours to days, with an increase in the overall symptom score, above the cut off, in at least 45% of GS subjects enrolled and that have received gluten compared to GS who received placebo.
Read the detailed description
Gluten is the most important protein component of some grains, notably wheat, rye, and barley, which are the basis for a variety of flour and wheat derived alimentary products consumed throughout the world (bread, pasta, pizza etc). However the "engineering" of gluten-containing grains created the conditions for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including wheat allergy, Gluten Sensitivity and Celiac Disease, that, combined, affect about 10% of the general population. The frequency of not-celiac gluten intolerance is however still unknown, even though it is possible that these conditions have been undiagnosed and under-diagnosed by the physicians for long time. The state of immune responsiveness to wheat antigens, represents a complex process, and its establishment and maintenance are not completely elucidated. The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, IgE-mediated allergic reactions and celiac disease (CD).
However, besides CD and wheat allergy, there are cases of gluten reactions in which neither allergic nor autoimmune mechanisms are involved. These are generally defined as gluten sensitivity (GS). Some individuals, who experience distress when eating gluten-containing products and show improvement when following a gluten-free diet, may have GS instead of CD. GS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten that usually, and differently from CD, does not lead to small intestinal damage. While the gastrointestinal symptoms in GS may resemble those associated with CD, the overall clinical picture is generally less severe and is not accompanied by the concurrence of tTG autoantibodies or autoimmune disease. Typically the diagnosis is made by exclusion, and an elimination diet and "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves with the elimination or reduction of gluten from the diet.
This has two major aims:
- Evaluation of the effective dependence from the gluten of the clinical alterations presented by subjects with gluten sensitivity (GS). The study will be done after a period of gluten-free diet (washout of 15 days), comparing two groups of GS subjects: given gluten or placebo (15 days), followed by a further period (15 days) on gluten free diet .
- identification of possible markers (serological, gut barrier function, immunological and expression of tight junctions constitutive proteins) that may be of help to differentiate, in humans, the condition of gluten sensitivity (GS) from that of Celiac Disease (CD); these markers might be of help in the early diagnosis of GS versus CD especially in the case of discordant serology.
- Conditions
- Gluten Sensitivity
- Being tested
- gluten, rice starch
- Keywords
- gluten sensitivity
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glutenDietary supplement
gluten is administered once a day at 10g/day for 15 days
rice starchDietary supplement
rice starch is administered once a day at 10 g/day for 15 days
| Study group | Role | What they receive |
|---|---|---|
| gluten | Active comparator | gluten is administered blindly versus placebo for 15 days at 10 g/day Receives: Dietary Supplement: gluten |
| rice starch | Placebo comparator | placebo (rice starch) will be administered blindly versus gluten for 15 days at 10 g/day Receives: Dietary Supplement: rice starch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptoms evaluation according to 3 scales: score after 2 weeks of gluten ingestion
The evaluation will be made according to the score calculated on the basis of three evaluation scales: "Gastrointestinal Symptom Rating Scale "(GSRS), modified, provides a score ranging MIN=15/MAX=60; Extra-gastrointestinal symptoms evaluation scale, proposed on the basis of the symptoms most frequently observed in GS patients, provides a score ranging MIN=9/MAX=34; VQV scale proposed to evaluate the quality of life, provides a score ranging MIN=16/MAX=64. Total score can be no less than 37 (MIN) and not more than 146 (MAX), with a cut-off of 55.
Measured: Change from baseline at 2 weeks
Secondary outcomes (2)
Bio-Markers to differentiate GS and CD
The identification of possible markers (serological, gut barrier function, immunological and expression of tight junctions constitutive proteins) that may be of help to differentiate, in humans, the condition of gluten sensitivity (GS) from that of Celiac Disease (CD); these markers might be of help in the early diagnosis of GS versus CD especially when the serology is discordant.
Measured: Change from baseline at 2 weeks
Symptoms evaluation according to 3 scales: scores 2 weeks after completion of intervention
The evaluation will be made according to the score calculated on the basis of three evaluation scales: "Gastrointestinal Symptom Rating Scale "(GSRS), modified, provides a score ranging MIN=15/MAX=60; Extra-gastrointestinal symptoms evaluation scale, proposed on the basis of the symptoms most frequently observed in GS patients, provides a score ranging MIN=9/MAX=34; VQV scale proposed to evaluate the quality of life, provides a score ranging MIN=16/MAX=64. Total score can be no less than 37 (MIN) and not more than 146 (MAX), with a cut-off of 55.
Measured: Return to baseline values at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2011 (estimated)
- Study startJun 2011
- Primary completionApr 2016
- Study completionApr 2016
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 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Laura de Magistris, University of Campania Luigi Vanvitelli
- Investigators
- Anna Sapone, MD, PhD, Principal investigator, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01485341
- Sponsor's protocol ID
- 61-2-9-2011
- Acronym
- GS
- Status last verified
- Apr 2016
- First submitted
- 17 Nov 2011
- Last updated
- 13 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Randomized Placebo Controlled Multicenter Trial (Gluten vs Placebo) in Gluten Sensitive Subjects
- ClinicalTrials.gov ID
- NCT01485341
- Acronym / sponsor ID
- GS / 61-2-9-2011
- Conditions
- Gluten Sensitivity
- Keywords
- gluten sensitivity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 5 Dec 2011 (estimated)
- 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 idea is to evaluate if the so called "Gluten Sensitivity" is a real clinical entity. Gluten sensitive (GS) persons are defined as those patients, being neither celiac or allergic to weat, who develop symptoms following gluten consumption. This will be achieved by evaluating a global symptom score in GS patients receiving gluten compared to those receiving placebo (primary end point). Symptoms to be evaluated: gastrointestinal (Gastrointestinal Symptom Rating Scale, GSRS); not-gastrointestinal (specifically built evaluation scale); VQV scale, built to evaluate quality of life. Gluten or placebo will be administered daily (10 g) for 15 days; for the 15 days before and 15 after all patients will stay on Gluten Free Diet (GFD). Besides clinical evaluation (each week for 6 weeks), intestinal permeability testing and blood sampling will be requested for the identification of possible markers (serological, gut barrier function, immunological and expression of tight junctions constitutive proteins) that may be of help to differentiate the condition of gluten sensitivity (GS) from that of Celiac Disease (CD)(secondary end point). Inclusion and exclusion criteria for patients enrolling are strictly dependant on the given "Gluten sensitivity" definition. We expect to experience a worsening of gastrointestinal and extra-gastrointestinal symptoms, from hours to days, with an increase in the overall symptom score, above the cut off, in at least 45% of GS subjects enrolled and that have received gluten compared to GS who received placebo.
Detailed description
Gluten is the most important protein component of some grains, notably wheat, rye, and barley, which are the basis for a variety of flour and wheat derived alimentary products consumed throughout the world (bread, pasta, pizza etc). However the "engineering" of gluten-containing grains created the conditions for human diseases related to gluten exposure. These forms of gluten intolerance represent a heterogeneous set of conditions, including wheat allergy, Gluten Sensitivity and Celiac Disease, that, combined, affect about 10% of the general population. The frequency of not-celiac gluten intolerance is however still unknown, even though it is possible that these conditions have been undiagnosed and under-diagnosed by the physicians for long time. The state of immune responsiveness to wheat antigens, represents a complex process, and its establishment and maintenance are not completely elucidated. The most frequent diseases caused by wheat ingestion are T cell-mediated disorders, IgE-mediated allergic reactions and celiac disease (CD).
However, besides CD and wheat allergy, there are cases of gluten reactions in which neither allergic nor autoimmune mechanisms are involved. These are generally defined as gluten sensitivity (GS). Some individuals, who experience distress when eating gluten-containing products and show improvement when following a gluten-free diet, may have GS instead of CD. GS patients are unable to tolerate gluten and develop an adverse reaction when eating gluten that usually, and differently from CD, does not lead to small intestinal damage. While the gastrointestinal symptoms in GS may resemble those associated with CD, the overall clinical picture is generally less severe and is not accompanied by the concurrence of tTG autoantibodies or autoimmune disease. Typically the diagnosis is made by exclusion, and an elimination diet and "open challenge" (i.e., the monitored reintroduction of gluten-containing foods) are most often used to evaluate whether health improves with the elimination or reduction of gluten from the diet.
This has two major aims:
- Evaluation of the effective dependence from the gluten of the clinical alterations presented by subjects with gluten sensitivity (GS). The study will be done after a period of gluten-free diet (washout of 15 days), comparing two groups of GS subjects: given gluten or placebo (15 days), followed by a further period (15 days) on gluten free diet .
- identification of possible markers (serological, gut barrier function, immunological and expression of tight junctions constitutive proteins) that may be of help to differentiate, in humans, the condition of gluten sensitivity (GS) from that of Celiac Disease (CD); these markers might be of help in the early diagnosis of GS versus CD especially in the case of discordant serology.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gluten | Active comparator | Dietary Supplement: glutengluten is administered blindly versus placebo for 15 days at 10 g/day |
| rice starch | Placebo comparator | Dietary Supplement: rice starchplacebo (rice starch) will be administered blindly versus gluten for 15 days at 10 g/day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult patients with age between 18-65 with signs/symptoms compatible with gluten-triggered disorders
- Patients testing negative for celiac disease either by biopsy Marsh 0-1 or those who are HLA-DQ2 and DQ8 negative, as well as tTG and EMA negative
- Patients that improved on a gluten free diet
Key exclusion criteria (6 listed)
- Subjects diagnosed with celiac disease (positive TTG and/or EMA, and histology positive with Marsh II or above);
- Subjects diagnosed with wheat allergy
- Subjects with Type 1 Diabetes (T1D)
- Subjects with Inflammatory Bowel Disease (ulcerative colitis or Crohn's disease)
- Pregnancy
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 |
|---|---|---|
| glutengluten is administered once a day at 10g/day for 15 days | Dietary supplement | gluten |
| rice starchrice starch is administered once a day at 10 g/day for 15 days | Dietary supplement | rice starch |
Primary outcome
Symptoms evaluation according to 3 scales: score after 2 weeks of gluten ingestion
Time frame: Change from baseline at 2 weeks
The evaluation will be made according to the score calculated on the basis of three evaluation scales: "Gastrointestinal Symptom Rating Scale "(GSRS), modified, provides a score ranging MIN=15/MAX=60; Extra-gastrointestinal symptoms evaluation scale, proposed on the basis of the symptoms most frequently observed in GS patients, provides a score ranging MIN=9/MAX=34; VQV scale proposed to evaluate the quality of life, provides a score ranging MIN=16/MAX=64. Total score can be no less than 37 (MIN) and not more than 146 (MAX), with a cut-off of 55.
2 secondary outcomes
Bio-Markers to differentiate GS and CD
Time frame: Change from baseline at 2 weeks
Symptoms evaluation according to 3 scales: scores 2 weeks after completion of intervention
Time frame: Return to baseline values at 4 weeks
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 13 Apr 2016.
Related trials for Gluten Sensitivity
Enrolling by invitation
Immune Responses to Gluten
Celiac Disease, Malabsorption Syndromes
RecruitingPhase 1
A First-in-Patient Study to Evaluate the Safety and Tolerability of HB-2121 as a Diagnostic for Celiac Disease
Celiac Disease
Recruiting
Urinary Gluten Immunogenic Peptides Detection in Non-celiac Gluten/Wheat Sensitivity
Non-celiac Gluten/Wheat Sensitivity
Recruiting
Single-cell Immune Response to Controlled Gluten Ingestion in Pediatric Celiac Disease
Celiac Disease, Gluten Sensitivity
Recruiting
Dietary Approach to Mild-to-moderate Psoriasis
Psoriasis, Gluten Sensitivity
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.
Anna Sapone, MD, PhD principal investigator
University of Campania Luigi Vanvitelli
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing gluten and rice starch in people with Gluten Sensitivity, run by University of Campania Luigi Vanvitelli at 7 sites in 2 countries.
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 3 inclusion and 6 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 13 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy, United States. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Symptoms evaluation according to 3 scales: score after 2 weeks of gluten ingestion (time frame: Change from baseline at 2 weeks). 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 13 Apr 2016.