Celiac Disease Diagnosis in Patients With Weakly Positive Serum Anti-Transglutaminase: Duodenal Anti-Endomysium Assay.

NCT02242123 | Completed

• 1 other identifier: ACPM05
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Celiac disease (CD) is a chronic immune-mediated disorder that occurs in genetically predisposed populations. Patients affected by the disease may be asymptomatic or manifest classic malabsorption symptoms of diarrhea, steatorrhea, abdominal pain, and weight loss after gluten ingestion (and related derivatives found in other grains). Diagnosis and screening begin with the use of serologic tests, i.e. IgA anti-tissue transglutaminase (tTG) and IgA anti-endomysial antibodies (EmA). Duodenal biopsy, still considered by many as the criterion necessary for diagnosis, demonstrates the pathologic findings of small intestinal villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis that occur on exposure to dietary gluten. Genetic tests, revealing permissive haplotypes, may be helpful in identifying susceptible individuals. CD diagnosis is still anchored to the criteria established by the European Society of Pediatric Gastroenterology Hepatology and Nutrition in 1990. These require the mandatory presence of (a) villous atrophy with crypt hyperplasia and increased intraepithelial lymphocytes (IELs) count when the patient is eating gluten, and (b) a full clinical remission after elimination of gluten from the diet. As a consequence, patients with minimal or no intestinal histology lesions pose a considerable problem, as serum anti-tTG and EmA are known to be often negative, or weakly positive, in patients with CD with mild intestinal damage. The investigators, in 2002, measured anti-tTG antibody in the culture medium of intestinal biopsy specimens from patients with suspected CD and evaluated the relationship between antibody production and severity of intestinal mucosal damage, and demonstrated that anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies. The same investigators, in 2011, evaluated the diagnostic accuracy of EmA assay in the culture medium of intestinal biopsies for CD diagnosis and demonstrated that EmA assay in the culture medium had a higher sensitivity and specificity than serum EmA and anti-tTG assay. The present study is performed to investigate the clinical usefulness of the in vitro production of EmA in CD diagnosis in a large number of consecutive adult patients with suspected CD and weakly positive \[e.g. 2-3xN\] serum anti-tTG.

Conditions

Celiac Disease

Keywords

Celiac Disease; Gluten-free diet; EmA assay; Duodenal culture medium

Outcome Measures

Primary Outcomes (1)

• Changes in the intestinal histology of the patients with clinically suspected CD and weakly positive [e.g. 2-3xN] serum anti-tTG antibodies, at the time of the first evaluation.

  Intestinal histology re-evaluation after at least one year after the first evaluation for suspected CD, without any dietary restriction. Marsh-Oberhuber's classification will be adopted: change from baseline (1st evaluation) to 2nd evaluation

  At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.

Secondary Outcomes (2)

• Serum IgA anti-tTG antibodies evaluation.

  At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.

• Symptoms/signs evaluation.

  At baseline (first evaluation) and after at least one year since the first evaluation for suspected CD.

Other Outcomes (2)

• EmA assay in duodenal biopsies evaluation.

  At the time of first duodenal histology evaluation.

• Human leukocyte antigen (HLA) evaluation.

  At baseline (first visit).

Study Arms (2)

Study group

Symptomatic patients, with weakly positive serum anti-tTG and evidence of mild intestinal histology damage (grade 1-2) at first evaluation.

Control group

Symptomatic patients, with weakly positive serum anti-tTG and evidence of intestinal villous atrophy (intestinal histology damage grade 3) at first evaluation.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study will include consecutive patients, referred to two centers in Palermo and Sciacca, at the Internal Medicine Department of the University Hospital of Palermo, and at the Internal Medicine Department of the Hospital of Sciacca (Agrigento), between January 2014 and June 2016.

You may qualify if:

• adult patients, both genders, aged between 18-70 years;
• with suspected CD (i.e. affected with one or more of the following symptoms: chronic diarrhea or constipation, alternating bowel habits, abdominal pain, dyspepsia, recurrent aphthosis, dental enamel defects, thyroiditis, dermatitis, osteoporosis, joints pain, weight loss, anemia, cryptogenetic hypertransaminasemia);
• with weakly positive \[e.g. 2-3xN\] serum anti-tTG antibodies; and d) subjects with a family history of CD.

You may not qualify if:

• \- patients with IgA deficiency, type 1 diabetes, inflammatory bowel diseases (Crohn's disease or ulcerative colitis), Helicobacter pylori infection and other gastrointestinal infection, and pregnancy.

Sponsors & Collaborators

• University of Palermo: lead

Study Sites (2)

Internal Medicine Department of the Hospital of Sciacca (Agrigento)

Sciacca, Agrigento, 92019, Italy

Location

Internal Medicine Department of the University Hospital of Palermo

Palermo, 90127, Italy

Location

Related Publications (4)

• Picarelli A, Maiuri L, Frate A, Greco M, Auricchio S, Londei M. Production of antiendomysial antibodies after in-vitro gliadin challenge of small intestine biopsy samples from patients with coeliac disease. Lancet. 1996 Oct 19;348(9034):1065-7. doi: 10.1016/S0140-6736(96)03060-7.

  PMID: 8874458 RESULT

• Carroccio A, Iacono G, D'Amico D, Cavataio F, Teresi S, Caruso C, Di PL, Colombo A, D'Arpa F, Florena A, Notarbartolo A, Montalto G. Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis. Scand J Gastroenterol. 2002 Jan;37(1):32-8. doi: 10.1080/003655202753387329.

  PMID: 11843032 RESULT

• Carroccio A, Iacono G, Di Prima L, Pirrone G, Cavataio F, Ambrosiano G, Sciume C, Geraci G, Florena A, Teresi S, Barbaria F, Pepe I, Campisi G, Mansueto P, Soresi M, Di Fede G. Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis. Eur J Gastroenterol Hepatol. 2011 Nov;23(11):1018-23. doi: 10.1097/MEG.0b013e328349b8a5.

  PMID: 21885984 RESULT

• Carroccio A, Di Prima L, Pirrone G, Scalici C, Florena AM, Gasparin M, Tolazzi G, Gucciardi A, Sciume C, Iacono G. Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis. Clin Chem. 2006 Jun;52(6):1175-80. doi: 10.1373/clinchem.2005.061366. Epub 2006 Mar 30.

  PMID: 16574764 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

Duodenal biopsy specimens

MeSH Terms

Conditions

Celiac Disease

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Antonio Carroccio, MD, PhD

  Internal Medicine Department of the Hospital of Sciacca (Agrigento)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 14, 2014
• First Posted: September 16, 2014
• Study Start: January 1, 2012
• Primary Completion: December 1, 2016
• Study Completion: June 1, 2020
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)