Celiac DiseaseGFDLNCT05733663
TCRγδ+ Cells After Gluten-free Diet: A Biomarker for Coeliac Disease?
An observational study of Celiac Disease, run by Hospital Mutua de Terrassa at 1 site in Spain.
Trial summary
Coeliac disease (CD) is a systemic process of autoimmune nature related to the existence of a permanent intolerance to gluten and manifests itself in genetically susceptible individuals. It has a global prevalence of 0.5-1.5%. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Endoscopic procedure with duodenal biopsy
- How many people
- 116 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jan 2013to 31 Dec 2020
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: * All patients included in the 'Prospective hospital registry of patients with suspected coeliac disease', who fulfil the inclusion criteria and none of the exclusion criteria in present study. * Study period: The study period will be 8 years (January 2013 - December 2020). * Diagnosis of CD will be based on the 2019-guidelines of the European Society for the Study of Coeliac Disease, and the recent Paris consensus criteria about diagnosis of seronegative CD. Presence of a compatible T-cell flow cytometric coeliac pattern will be considered as complementary for diagnosis of seronegative CD.
Who may be able to join
- Paediatric or adult patients diagnosed with CD and started on a strict GFD
- Patients with a follow-up intestinal biopsy to assess histological remission at least 1-year after starting the GFD
- Assessment of the intraepithelial lymphogram at both baseline and follow-up
- Presence of increased TCRγδ+ cells at baseline.
Who cannot join
- Refusal of the patient to participate in the registry.
- Pregnancy and severe comorbidities (heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc).
- Patients with intake of NSAIDs or Olmesartan.
- Patients with Crohn's disease, autoimmune disease associated enteropathy, collagenous sprue, microscopic colitis, lymphocytic enteritis due to intestinal parasitosis or Helicobacter pylori infection, other enteropathies.
- Selective IgA deficiency.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Persistent Increase in the Intestinal γδ+ T-cell Subset: A Potential Biomarker of Coeliac Disease in Patients Started on a Gluten-free Diet
Coeliac disease (CD) is a systemic process of autoimmune nature related to the existence of a permanent intolerance to gluten and manifests itself in genetically susceptible individuals. It has a global prevalence of 0.5-1.5%. The diagnosis of CD should be made in patients following a normal gluten-containing diet and is based on coeliac serology and histopathological changes of the small intestinal mucosa. However, nowadays many patients come to their doctor to rule out CD after having started a gluten-free diet (GFD) with improvement of symptoms. In this scenario, making the diagnosis of CD remains a challenge, as it must be considered that most CD-associated changes revert after gluten withdrawal.
An essential finding of CD is the increased number in total intraepithelial lymphocytes (IEL) in the duodenal mucosa, later characterized by an expansion of γδ+ and CD8+ IEL coupled to a decrease in CD3- IEL. An accurate quantification of the γδ+ subset became possible with the introduction of flow cytometry. In 2002, Spanish investigators proposed a diagnostic algorithm for paediatric CD that included the combined use of a high percentage of γδ+ and a low percentage of CD3- IEL, which was termed the coeliac lymphogram, which has been shown to be very accurate for the diagnosis of CD. Thus, the use of flow cytometric phenotyping of IEL may strengthen the diagnosis of CD when it is not straightforward.
This study will provide information about the potential usefulness of T-cell flow cytometric coeliac patterns as CD biomarkers to confirm the diagnosis of CD in patients who have already started a GFD. These results may help to make decisions in specific situations of routine clinical practice, avoiding bothersome gluten reintroduction and delays in diagnosis.
Read the detailed description
Hypothesis:
The increase in the TCRγδ+ subset appears to be permanent despite a GFD, which opens up the possibility of using it as a diagnostic tool in patients following a GFD, without the need to undergo gluten challenge. Several studies have focused on this aspect with promising results, but the studies have been performed on small samples of patients, and follow-up time after a GFD has not always been described or only changes in mean values before versus after the diet have been reported.
- Conditions
- Celiac Disease
- Being tested
- Endoscopic procedure with duodenal biopsy
- Keywords
- Coeliac disease, Gluten-free diet, Intraepithelial lymphocytes, Villous atrophy
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endoscopic procedure with duodenal biopsyDiagnostic test
- In all patients the investigators will analyse coeliac serology, DQ-genotype, and results of two duodenal biopsy sampling (one at diagnosis before starting the GFD and another sampling during follow-up with GFD) for assessment of both histopathology and intraepithelial lymphocyte subpopulations by T-cell flow cytometry. In addition, clinical, serological, and histological response to GFD will be evaluated.
- T-cell flow cytometry assay is performed as previously described by our group in previous studies. In all patients, an additional duodenal biopsy sample is taken from the second-third portion of the duodenum at the same endoscopic procedure that for histopathology. The normal cut-off values for the IEL cytometric pattern in our laboratory are CD3+TCRγδ+ IEL ≤8.5% (≤mean + 2SD) and CD3- IEL ≥10% (10th percentile). The cut-offs define four intraepithelial lymphogram patterns: normal, isolated decrease in CD3- cells, isolated increase in TCRγδ+ cells, and the coeliac lymphogram.
| Study group | Role | What they receive |
|---|---|---|
| Adult patients diagnosed with coeliac disease | A group of paediatric or adult patients diagnosed with CD and started on a strict GFD, with baseline and a follow-up intestinal biopsy to assess histological and intraepithelial lymphogram at least 1-year after starting the GFD, and with increased γδ+ T-cells at baseline. Receives: Diagnostic Test: Endoscopic procedure with duodenal biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of long-term persistence of both the coeliac lymphogram (increase in TCRγδ+ and decrease in CD3- cells) and the isolated increase in TCRγδ+ cells measured by T-cell flow cytometry in CD patients after starting a GFD.
Lymphocyte subpopulations (TCRγδ+ and CD3- cells) are measured by flow cytometry.
Measured: 1 year
Secondary outcomes (6)
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to baseline histology (measured by Marsh Classification: 0, 1, 2 or 3)
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to age group (measured by years).
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to gender (classified according to male or female sex).
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to coeliac serology (measured by presence or absence of anti-transglutaminase antibodies).
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to DQ-genotype (measured by presence or absence of HLA-DQ2.5).
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to follow-up time (measured by years).
To assess the frequency of nonpersistence of the increased TCRγδ+ subset related to study variables, the chi-square test, Fisher exact test, and the Freeman-Halton extension of the Fisher exact probability test for a 2x3 or a 2x4 contingency table were used.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2023
- Study start1 Jan 2013
- Primary completion1 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Celiac DiseaseStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Mutua de Terrassa
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maria Esteve, PhD, MD, Principal investigator, Hospital Universitari Mútua Terrassa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05733663
- Sponsor's protocol ID
- GFDL
- Acronym
- GFDL
- Status last verified
- Apr 2023
- First submitted
- 8 Feb 2023
- Last updated
- 6 Apr 2023
- 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 6 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Persistent Increase in the Intestinal γδ+ T-cell Subset: A Potential Biomarker of Coeliac Disease in Patients Started on a Gluten-free Diet
- ClinicalTrials.gov ID
- NCT05733663
- Acronym / sponsor ID
- GFDL / GFDL
- Conditions
- Celiac Disease
- Keywords
- Coeliac disease, Gluten-free diet, Intraepithelial lymphocytes, Villous atrophy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Hospital Mutua de TerrassaUniversity, hospital or other
- Study start
- 1 Jan 2013 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 17 Feb 2023 (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.
Coeliac disease (CD) is a systemic process of autoimmune nature related to the existence of a permanent intolerance to gluten and manifests itself in genetically susceptible individuals. It has a global prevalence of 0.5-1.5%. The diagnosis of CD should be made in patients following a normal gluten-containing diet and is based on coeliac serology and histopathological changes of the small intestinal mucosa. However, nowadays many patients come to their doctor to rule out CD after having started a gluten-free diet (GFD) with improvement of symptoms. In this scenario, making the diagnosis of CD remains a challenge, as it must be considered that most CD-associated changes revert after gluten withdrawal.
An essential finding of CD is the increased number in total intraepithelial lymphocytes (IEL) in the duodenal mucosa, later characterized by an expansion of γδ+ and CD8+ IEL coupled to a decrease in CD3- IEL. An accurate quantification of the γδ+ subset became possible with the introduction of flow cytometry. In 2002, Spanish investigators proposed a diagnostic algorithm for paediatric CD that included the combined use of a high percentage of γδ+ and a low percentage of CD3- IEL, which was termed the coeliac lymphogram, which has been shown to be very accurate for the diagnosis of CD. Thus, the use of flow cytometric phenotyping of IEL may strengthen the diagnosis of CD when it is not straightforward.
This study will provide information about the potential usefulness of T-cell flow cytometric coeliac patterns as CD biomarkers to confirm the diagnosis of CD in patients who have already started a GFD. These results may help to make decisions in specific situations of routine clinical practice, avoiding bothersome gluten reintroduction and delays in diagnosis.
Detailed description
Hypothesis:
The increase in the TCRγδ+ subset appears to be permanent despite a GFD, which opens up the possibility of using it as a diagnostic tool in patients following a GFD, without the need to undergo gluten challenge. Several studies have focused on this aspect with promising results, but the studies have been performed on small samples of patients, and follow-up time after a GFD has not always been described or only changes in mean values before versus after the diet have been reported.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adult patients diagnosed with coeliac disease | – | Diagnostic Test: Endoscopic procedure with duodenal biopsyA group of paediatric or adult patients diagnosed with CD and started on a strict GFD, with baseline and a follow-up intestinal biopsy to assess histological and intraepithelial lymphogram at least 1-year after starting the GFD, and with increased γδ+ T-cells at baseline. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- * All patients included in the 'Prospective hospital registry of patients with suspected coeliac disease', who fulfil the inclusion criteria and none of the exclusion criteria in present study. * Study period: The study period will be 8 years (January 2013 - December 2020). * Diagnosis of CD will be based on the 2019-guidelines of the European Society for the Study of Coeliac Disease, and the recent Paris consensus criteria about diagnosis of seronegative CD. Presence of a compatible T-cell flow cytometric coeliac pattern will be considered as complementary for diagnosis of seronegative CD.
Key inclusion criteria (4 listed)
- Paediatric or adult patients diagnosed with CD and started on a strict GFD
- Patients with a follow-up intestinal biopsy to assess histological remission at least 1-year after starting the GFD
- Assessment of the intraepithelial lymphogram at both baseline and follow-up
- Presence of increased TCRγδ+ cells at baseline.
Key exclusion criteria (5 listed)
- Refusal of the patient to participate in the registry.
- Pregnancy and severe comorbidities (heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc).
- Patients with intake of NSAIDs or Olmesartan.
- Patients with Crohn's disease, autoimmune disease associated enteropathy, collagenous sprue, microscopic colitis, lymphocytic enteritis due to intestinal parasitosis or Helicobacter pylori infection, other enteropathies.
- Selective IgA deficiency.
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 |
|---|---|---|
| Endoscopic procedure with duodenal biopsy* In all patients the investigators will analyse coeliac serology, DQ-genotype, and results of two duodenal biopsy sampling (one at diagnosis before starting the GFD and another sampling during follow-up with GFD) for assessment of both histopathology and intraepithelial lymphocyte subpopulations by T-cell flow cytometry. In addition, clinical, serological, and histological response to GFD will be evaluated. * T-cell flow cytometry assay is performed as previously described by our group in previous studies. In all patients, an additional duodenal biopsy sample is taken from the second-third portion of the duodenum at the same endoscopic procedure that for histopathology. The normal cut-off values for the IEL cytometric pattern in our laboratory are CD3+TCRγδ+ IEL ≤8.5% (≤mean + 2SD) and CD3- IEL ≥10% (10th percentile). The cut-offs define four intraepithelial lymphogram patterns: normal, isolated decrease in CD3- cells, isolated increase in TCRγδ+ cells, and the coeliac lymphogram. | Diagnostic test | Adult patients diagnosed with coeliac disease |
Primary outcome
Percentage of long-term persistence of both the coeliac lymphogram (increase in TCRγδ+ and decrease in CD3- cells) and the isolated increase in TCRγδ+ cells measured by T-cell flow cytometry in CD patients after starting a GFD.
Time frame: 1 year
Lymphocyte subpopulations (TCRγδ+ and CD3- cells) are measured by flow cytometry.
6 secondary outcomes
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to baseline histology (measured by Marsh Classification: 0, 1, 2 or 3)
Time frame: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to age group (measured by years).
Time frame: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to gender (classified according to male or female sex).
Time frame: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to coeliac serology (measured by presence or absence of anti-transglutaminase antibodies).
Time frame: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to DQ-genotype (measured by presence or absence of HLA-DQ2.5).
Time frame: 1 year
Percentage of loss of the T-cell flow cytometric coeliac pattern (increase in TCRγδ+) according to follow-up time (measured by years).
Time frame: 1 year
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 6 Apr 2023.
- 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.
Maria Esteve, PhD, MD principal investigator
Hospital Universitari Mútua Terrassa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Celiac Disease, run by Hospital Mutua de Terrassa at 1 site in Spain.
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 4 inclusion and 5 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 6 Apr 2023. 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 Spain. 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. 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?
Percentage of long-term persistence of both the coeliac lymphogram (increase in TCRγδ+ and decrease in CD3- cells) and the isolated increase in TCRγδ+ cells measured by T-cell flow cytometry in CD patients after starting a GFD. (time frame: 1 year). 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 6 Apr 2023.