Intestinal Transglutaminase Antibodies in Celiac Disease Diagnosis

Celiac Disease Clinical Trial

Official title:

Use of Intestinal Transglutaminase Antibodies in the Diagnosis of Celiac Disease in Children and Adults: a Multicenter Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05810441
• Other study ID #: RC 04/19
• Status: Completed
• Start date: September 23, 2019
• Est. completion date: December 31, 2022

Study information

• Verified date: April 2023
• Source: IRCCS Burlo Garofolo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 213
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Celiac Disease

Intervention

Other:
• Evaluation of diagnostic accuracy of anti-ttg-m
Mucosal anti-ttg evaluated in intestinal biopsy samples

Locations

Country	Name	City	State
Italy	IRCCS materno infantile Burlo Garofolo	Trieste

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Burlo Garofolo

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	At the time of intestinal biopsy
Primary	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	At the time of intestinal biopsy
Secondary	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.	At the time of intestinal biopsy
Secondary	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	After 12 months of gluten-free diet