Celiac DiseaseNCT05810441
Intestinal Transglutaminase Antibodies in Celiac Disease Diagnosis
An observational study of Celiac Disease, run by IRCCS Burlo Garofolo at 1 site in Italy.
Trial summary
Celiac disease (CD) is a systemic autoimmune gluten-dependent enteropathy in subjects with HLA DQ2/8. CD prevalence is more than 1% with a progression to 2% in adulthood. Among the group at risk such as first-degree relatives, subjects with autoimmune diseases (eg type 1 diabetes) or with syndromes (Down's disease… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Celiac Disease
- What is being tested?
- Evaluation of diagnostic accuracy of anti-ttg-m
- How many people
- 213 participants
- Where
- 1 siteItaly
- Study dates
- 23 Sep 2019to 31 Dec 2022
- 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: Pediatric and adult subject. Subjects with clinical suspicion of CD; asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD; subjects undergoing gastro-intestinal endoscopy for infectious, oncologic or inflammatory disorders
Who may be able to join
- Pediatric and adult subjects
- Subjects with clinical suspicion of CD, positive serum anti-ttg concentrations with any value or type of presentation (permanent or fluctuating)
- Asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD (eg family members of CD patients, subjects with autoimmune diseases)
- Subjects undergoing gastro-intestinal endoscopy for infectious (eg Helicobacter pylori gastritis), oncologic (tumors of the gastro intestinal tract) or inflammatory disorders (Crohn disease, ulcerative colitis, eosinophilic esophagitis) in acute phase or in remission
Who cannot join
- Subjects in whom to take biopsies is not indicated during the gastro-intestinal endoscopy
- Subjects with oncological pathology undergoing chemotherapy treatment because anti-blastic agents may play an inhibitory activity in the production of immunoglobulins
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Use of Intestinal Transglutaminase Antibodies in the Diagnosis of Celiac Disease in Children and Adults: a Multicenter Prospective Study
Celiac disease (CD) is a systemic autoimmune gluten-dependent enteropathy in subjects with HLA DQ2/8. CD prevalence is more than 1% with a progression to 2% in adulthood. Among the group at risk such as first-degree relatives, subjects with autoimmune diseases (eg type 1 diabetes) or with syndromes (Down's disease, Turner) the prevalence reaches 5-8%. Recently, in pediatrics CD diagnostic criteria have been modified and the intestinal biopsy can be omitted in presence of a specific clinical and laboratory picture. In the remaining pediatric cases and in all adult patients, the biopsy is fundamental for the diagnosis. The clinical manifestation of CD not always depends on the enteropathy and on the related symptoms, but it can be characterized by extra-intestinal symptoms (eg chronic fatigue, anemia, arthralgia, cerebellar ataxia, alterations of dental enamel) that often hamper a rapid CD recognition delaying the diagnosis especially in adults. Symptoms are not always related to intestinal injury and may be present even when intestinal mucosa is normal. This condition is known as potential CD in which serum IgA anti-transglutaminase antibodies (anti-ttg) are generally positive at low concentrations (eg higher 2-3 times than the cut-off) or positive occasionally. In this clinical context, the gluten-free diet is an effective therapy able to improve the clinical picture and to stop the anti-ttg production. Recent observations, especially in pediatric field, have shown that in potential CD the immunological analysis of intestinal biopsies is characterized by the presence of anti-ttg deposits in the intestinal mucosa which predict the development of intestinal atrophy in a time span of 3- 5 years. Furthermore, these deposits disappear with the diet-therapy. In pediatric field, the diagnostic specificity of mucosal anti-ttg (anti-ttg-m) is between 95-98%, while the sensitivity is 100%. In adults, anti-ttg-m show 100% sensitivity in typical celiac disease (characterized by high serum anti-ttg concentrations and intestinal mucosa atrophy), while no results are available about potential celiac disease. Moreover, in adults data about the specificity of anti-ttg-m in infectious, oncological and inflammatory diseases of the gastro-intestinal tract are not available. The main study objectives are to evaluate anti-ttg-m sensitivity in patients with typical celiac disease and anti-ttg-m specificity in patients with oncological and inflammatory bowel diseases.
- Conditions
- Celiac Disease
- Being tested
- Evaluation of diagnostic accuracy of anti-ttg-m
- Keywords
- Celiac disease,, Mucosal anti-ttg, Intestinal biopsy culture
- Medical subject headings
- Celiac Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Evaluation of diagnostic accuracy of anti-ttg-mOther
Mucosal anti-ttg evaluated in intestinal biopsy samples
| Study group | Role | What they receive |
|---|---|---|
| Typical celiac disease | * symptomatic subjects (gastro-intestinal or extra-intestinal symptoms) tested positive for serum anti-ttg concentrations and with pathological intestinal biopsy;
* symptomatic and asymptomatic subjects at risk of CD (first-degree relatives of CD patients or subjects with autoimmune disorders) tested positive serum CD antibodies and with atrophic intestinal mucosa Receives: Other: Evaluation of diagnostic accuracy of anti-ttg-m | |
| Potential celiac disease | Symptomatic subjects tested positive for both serum CD antibodies and anti-ttg-m but with normal intestinal mucosa Receives: Other: Evaluation of diagnostic accuracy of anti-ttg-m | |
| Control group | Adult and pediatric subjects with inflammatory gastro-intestinal disorders (Crohn disease and ulcerative colitis in acute phase or in remission), oncologic diseases (tumors of the gastro intestinal tract) and infectious diseases (eg Helicobacter pylori gastritis) tested negative for serum anti-ttg Receives: Other: Evaluation of diagnostic accuracy of anti-ttg-m |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the sensitivity of anti-ttg-m for the diagnosis of typical celiac disease in adult and pediatric subjects
Anti-ttg-m will be evaluated using direct immunofluorescence and biopsy culture assays. For direct immunofluorescence technique: cryosections of intestinal tissue will be incubated with anti-ttg antibody labeled with rhodamine and subsequently with an antibody against human IgA conjugated with fluorescein. The cryosections will be analyzed with a fluorescence microscope equipped with a software to localize the overlap between red (rhodamine) and green (fluorescein) signals of the two antibodies. For intestinal biopsy culture: biopsies will be maintained in culture medium for 72 hours at 37 °C in the presence of soluble gliadin fragments. After 72 hours the culture liquid will be centrifuged and analyzed for the presence of anti-ttg and anti-endomysium by means of ELISA immuno-enzymatic technique and indirect immunofluorescence assay, respectively. Sensitivity will be evaluated in subjects with typical celiac disease
Measured: At the time of intestinal biopsy
To evaluate the specificity of anti-ttg-m in the control group
Anti-ttg-m will be evaluated as described in Outcome 1. Evaluation of specificity will be carried out in subjects with inflammatory diseases (Crohn disease, ulcerative colitis, in acute phase or in remission) or with oncological pathology at gastro-intestinal level or with infectious disease (Helicobacter pylori) tested negative for serum anti-ttg
Measured: At the time of intestinal biopsy
Secondary outcomes (2)
To compare immunofluorescence technique and biopsy culture assay in searching anti-ttg-m
Anti-ttg-m will be evaluated as described in Outcome 1. Results from immunofluorescence technique and biopsy culture assay will be compared.
Measured: At the time of intestinal biopsy
To demonstrate the gluten-dependence of anti-ttg-m in potential CD patients by searching anti-ttg-m after gluten-free diet
Anti-ttg-m will be evaluated as described in Outcome 1 in a second biopsy after a period of gluten-free diet
Measured: After 12 months of gluten-free diet
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2023
- Study start23 Sep 2019
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
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
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS Burlo Garofolo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chiara Zanchi, MD, Principal investigator, IRCCS materno infantile Burlo Garofolo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05810441
- Sponsor's protocol ID
- RC 04/19
- Status last verified
- Apr 2023
- First submitted
- 29 Mar 2023
- Last updated
- 12 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Intestinal Transglutaminase Antibodies in the Diagnosis of Celiac Disease in Children and Adults: a Multicenter Prospective Study
- ClinicalTrials.gov ID
- NCT05810441
- Acronym / sponsor ID
- RC 04/19
- Conditions
- Celiac Disease
- Keywords
- Celiac disease,, Mucosal anti-ttg, Intestinal biopsy culture
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- IRCCS Burlo GarofoloUniversity, hospital or other
- Study start
- 23 Sep 2019 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 12 Apr 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.
Celiac disease (CD) is a systemic autoimmune gluten-dependent enteropathy in subjects with HLA DQ2/8. CD prevalence is more than 1% with a progression to 2% in adulthood. Among the group at risk such as first-degree relatives, subjects with autoimmune diseases (eg type 1 diabetes) or with syndromes (Down's disease, Turner) the prevalence reaches 5-8%. Recently, in pediatrics CD diagnostic criteria have been modified and the intestinal biopsy can be omitted in presence of a specific clinical and laboratory picture. In the remaining pediatric cases and in all adult patients, the biopsy is fundamental for the diagnosis. The clinical manifestation of CD not always depends on the enteropathy and on the related symptoms, but it can be characterized by extra-intestinal symptoms (eg chronic fatigue, anemia, arthralgia, cerebellar ataxia, alterations of dental enamel) that often hamper a rapid CD recognition delaying the diagnosis especially in adults. Symptoms are not always related to intestinal injury and may be present even when intestinal mucosa is normal. This condition is known as potential CD in which serum IgA anti-transglutaminase antibodies (anti-ttg) are generally positive at low concentrations (eg higher 2-3 times than the cut-off) or positive occasionally. In this clinical context, the gluten-free diet is an effective therapy able to improve the clinical picture and to stop the anti-ttg production. Recent observations, especially in pediatric field, have shown that in potential CD the immunological analysis of intestinal biopsies is characterized by the presence of anti-ttg deposits in the intestinal mucosa which predict the development of intestinal atrophy in a time span of 3- 5 years. Furthermore, these deposits disappear with the diet-therapy. In pediatric field, the diagnostic specificity of mucosal anti-ttg (anti-ttg-m) is between 95-98%, while the sensitivity is 100%. In adults, anti-ttg-m show 100% sensitivity in typical celiac disease (characterized by high serum anti-ttg concentrations and intestinal mucosa atrophy), while no results are available about potential celiac disease. Moreover, in adults data about the specificity of anti-ttg-m in infectious, oncological and inflammatory diseases of the gastro-intestinal tract are not available. The main study objectives are to evaluate anti-ttg-m sensitivity in patients with typical celiac disease and anti-ttg-m specificity in patients with oncological and inflammatory bowel diseases.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Typical celiac disease | – | Other: Evaluation of diagnostic accuracy of anti-ttg-m* symptomatic subjects (gastro-intestinal or extra-intestinal symptoms) tested positive for serum anti-ttg concentrations and with pathological intestinal biopsy; * symptomatic and asymptomatic subjects at risk of CD (first-degree relatives of CD patients or subjects with autoimmune disorders) tested positive serum CD antibodies and with atrophic intestinal mucosa |
| Potential celiac disease | – | Other: Evaluation of diagnostic accuracy of anti-ttg-mSymptomatic subjects tested positive for both serum CD antibodies and anti-ttg-m but with normal intestinal mucosa |
| Control group | – | Other: Evaluation of diagnostic accuracy of anti-ttg-mAdult and pediatric subjects with inflammatory gastro-intestinal disorders (Crohn disease and ulcerative colitis in acute phase or in remission), oncologic diseases (tumors of the gastro intestinal tract) and infectious diseases (eg Helicobacter pylori gastritis) tested negative for serum anti-ttg |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Pediatric and adult subject. Subjects with clinical suspicion of CD; asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD; subjects undergoing gastro-intestinal endoscopy for infectious, oncologic or inflammatory disorders
Key inclusion criteria (4 listed)
- Pediatric and adult subjects
- Subjects with clinical suspicion of CD, positive serum anti-ttg concentrations with any value or type of presentation (permanent or fluctuating)
- Asymptomatic or pauci-symptomatic subjects tested positive for serum anti-ttg antibodies during screening test because at risk of CD (eg family members of CD patients, subjects with autoimmune diseases)
- Subjects undergoing gastro-intestinal endoscopy for infectious (eg Helicobacter pylori gastritis), oncologic (tumors of the gastro intestinal tract) or inflammatory disorders (Crohn disease, ulcerative colitis, eosinophilic esophagitis) in acute phase or in remission
Key exclusion criteria (2 listed)
- Subjects in whom to take biopsies is not indicated during the gastro-intestinal endoscopy
- Subjects with oncological pathology undergoing chemotherapy treatment because anti-blastic agents may play an inhibitory activity in the production of immunoglobulins
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 |
|---|---|---|
| Evaluation of diagnostic accuracy of anti-ttg-mMucosal anti-ttg evaluated in intestinal biopsy samples | Other | Control group, Potential celiac disease, Typical celiac disease |
Primary outcome
To evaluate the sensitivity of anti-ttg-m for the diagnosis of typical celiac disease in adult and pediatric subjects
Time frame: At the time of intestinal biopsy
Anti-ttg-m will be evaluated using direct immunofluorescence and biopsy culture assays. For direct immunofluorescence technique: cryosections of intestinal tissue will be incubated with anti-ttg antibody labeled with rhodamine and subsequently with an antibody against human IgA conjugated with fluorescein. The cryosections will be analyzed with a fluorescence microscope equipped with a software to localize the overlap between red (rhodamine) and green (fluorescein) signals of the two antibodies. For intestinal biopsy culture: biopsies will be maintained in culture medium for 72 hours at 37 °C in the presence of soluble gliadin fragments. After 72 hours the culture liquid will be centrifuged and analyzed for the presence of anti-ttg and anti-endomysium by means of ELISA immuno-enzymatic technique and indirect immunofluorescence assay, respectively. Sensitivity will be evaluated in subjects with typical celiac disease
To evaluate the specificity of anti-ttg-m in the control group
Time frame: At the time of intestinal biopsy
Anti-ttg-m will be evaluated as described in Outcome 1. Evaluation of specificity will be carried out in subjects with inflammatory diseases (Crohn disease, ulcerative colitis, in acute phase or in remission) or with oncological pathology at gastro-intestinal level or with infectious disease (Helicobacter pylori) tested negative for serum anti-ttg
2 secondary outcomes
To compare immunofluorescence technique and biopsy culture assay in searching anti-ttg-m
Time frame: At the time of intestinal biopsy
To demonstrate the gluten-dependence of anti-ttg-m in potential CD patients by searching anti-ttg-m after gluten-free diet
Time frame: After 12 months of gluten-free diet
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 12 Apr 2023.
- Individual participant dataSharing planned: Undecided
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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.
Chiara Zanchi, MD principal investigator
IRCCS materno infantile Burlo Garofolo
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 IRCCS Burlo Garofolo 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 4 inclusion and 2 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 12 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 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. 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?
To evaluate the sensitivity of anti-ttg-m for the diagnosis of typical celiac disease in adult and pediatric subjects (time frame: At the time of intestinal biopsy). The study lists 2 primary outcomes in all. 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 12 Apr 2023.