Histopathologic and Lymphocyte Subpopulations Evaluation of the Upper Gastrointestinal Tract of Crohn's Disease

Crohn Disease Clinical Trial

— CROHNLY  

Official title:

Histopathologic and Lymphocyte Subpopulations Evaluation of the Upper Gastrointestinal Tract of Crohn's Disease: A Multicentre Prospective Study (CROHNLY Project)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05874349
• Other study ID #: CROHNLY23
• Status: Completed
• Start date: June 1, 2017
• Est. completion date: January 1, 2023

Study information

• Verified date: May 2023
• Source: Hospital Mutua de Terrassa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Inflammatory bowel disease (IBD) comprises a series of disorders of unknown cause, such as ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC), associated with an over-the-top immune response that produces lesions of variable depth and extent in the intestine. They have a chronic course, without cure and with an unpredictable evolution. Clinical symptoms of CD are characterized by malaise, weight loss, fever, diarrhoea, abdominal pain, vomiting, sometimes palpable mass, perianal disease, among others. The disease is most frequently located in the ileocecal area, but all the entire digestive tract from the oral cavity to the rectum may be affected. The involvement of the upper gastrointestinal tract (UGT) (L4) in CD is frequently undiagnosed. From 1-7% of patients with CD refer symptoms or signs that are due to UG involvement. Chronic iron deficient anaemia, in the absence of digestive symptoms, is the only guiding sign that may alert about the diagnosis.

Furthermore, retrospective cohort studies suggest that CD of the UGT is associated with a worse prognosis. The systematic study of the UGT in the initial evaluation of CD at the time of diagnosis is not generally recommended in adulthood, European Crohn's and Colitis Organisation (ECCO) guidelines recommend upper endoscopy only if there are upper digestive symptoms (vomiting, dyspepsia, etc.). In the case of gastroscopy, gastric biopsies have to be performed due to the possible presence of focal active gastritis, which is considered very specific of CD. This statement is based on a limited series of cases published in 1980. On the other hand, systematic performance of duodenal biopsies is not recommended. This fact has caused that the histopathology of duodenal CD is very unknown and the need to perform duodenal biopsies of the UGT is still a matter of debate.

Macro and microscopic findings from the UGT have generally been used to differentiate between UC and CD in cases of IC. Among the macroscopic findings highlight the presence of sores or ulcers and most specific and frequent microscopic findings are granulomas and chronic inflammatory infiltrate respectively. However, it is known that CD can cause lymphocytic infiltration of the duodenal epithelium (duodenal lymphocytosis or lymphocytic enteritis) and villus atrophy. These are findings are characteristically found in celiac disease, and therefore, these histological lesions of the duodenum also propose the differential diagnosis between celiac disease and CD.

In addition, it must be considered that many of the patients with IBD take immunosuppressive for disease control, which have been reported to be the cause of lymphocytic enteritis and duodenal villus atrophy. This proposed drug-induced enteropathy is based only in a few series of cases in the context of treatment with azathioprine and methotrexate. There are no studies systematically evaluate how often these drugs can cause a "sprue like" enteropathy.

The lymphocytic enteritis of celiac disease has been associated with a specific pattern of lymphocyte subpopulations (increase in the percentage of CD3+TCRγẟ+ lymphocytes and decrease in the percentage of CD3-). It is unknown if CD duodenal lymphocytes is associated with a specific CD cytometric pattern. If so, the evaluation of lymphocyte subpopulations could be of great diagnostic aid when considering the differential diagnosis between celiac disease, CD and other forms of duodenal lymphocytosis.

Description:

Hypothesis:

Routine evaluation of the upper digestive tract mucosa can be useful for the differential diagnosis between of adult CD and celiac disease, particularly in patients with chronic iron-deficient anemia and lymphocytic enteritis in the duodenum. The study of the lymphocytic subpopulations can help in the differential diagnosis of lymphocytic enteritis and identify in which cases are due to CD. Nowadays, the prevalence of "sprue-like" enteropathy associated with the use of immunosuppressants in CD is unknown.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: January 1, 2023
• Est. primary completion date: June 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (> 18 years)

• Diagnosis of Crohn disease

• Diagnosis of Coeliac disease

• Control subjects

• Study period: The study period has been 36 months (June 2017 - June 2020)

Exclusion Criteria:

• Refusal of the patient to participate in the study

• Pregnancy

• Serious comorbidities: heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc

Related Conditions & MeSH terms

• Crohn Disease

Intervention

Behavioral:
• General variables
Variables evaluated: age, sex, location, extent, and phenotype of IBD according to the Montreal classification, smoking habit, therapeutic requirements (immunosuppressants, biologics, steroids, salicylates, drugs that cause enteropathy such as olmesartan, valsartan, non-steroidal anti-inflammatory drugs, etc, ...).
• Clinical activity
Clinical activity was evaluated using the Harvey-Bradshaw index (HBI) (cut-off values: <5, remission; 5-7, mild activity; 8-16, moderate activity; and >16, severe activity).

Procedure:
• Laboratory data
Laboratory data: blood count, renal function and C-reactive protein, anti-transglutaminase antibodies, genetic study of celiac disease DQ2.5, DQ8, and DQ2.2, study of parasites, fecal calprotectin.
• Endoscopic and histology data
Endoscopic signs suggestive of CD in UDT (presence of canker sores, ulcers, ...) and colon inflammatory activity was evaluated when available in patients with active disease using the Simple Endoscopic Score for CD (SES-CD: 0-2, remission; 3-6, mild endoscopic activity; 7-15, moderate endoscopic activity; and >15, severe endoscopic activity). Duodenal biopsies were assessed by 2 pathologists and were evaluated according to Marsh classification modified by Ensari [Marsh 0, 1, 2 or 3], the limit of normality for intraepithelial lymphocytes (IELs) per 100 enterocytes is set at 25, gastric biopsies (determination of H. Pylori by immunohistochemistry) and esophageal biopsies was recorded too. Percentage of lymphocyte subpopulations are assessed by flow cytometry.

Locations

Country	Name	City	State
Spain	Hospital Universitari Mutua Terrassa	Terrassa	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Mutua de Terrassa

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Description of microscopic lesions in the upper digestive tract in patients with CD.	Microscopic duodenum lesions are measured by "Marsh classification modified by Ensari" of histologic findings: Type 0: normal (<25 intraepithelial lymphocytes per 100 enterocytes).; Type 1: increased intraepithelial lymphocytes but no villous atrophy (>25 intraepithelial lymphocytes per 100 enterocytes).; Type 2: villi still present but shortened.; Type 3: complete villous atrophy.	3 years
Secondary	Percentage of lymphocyte subpopulations in the duodenum of patients with CD.	Percentage of lymphocyte subpopulations are assessed by flow cytometry.	3 years
Secondary	Description of "sprue-like" enteropathy associated with the use of immunosuppressants in CD.	"sprue-like" enteropathy lesions are measured by "Marsh classification modified by Ensari" of histologic findings: Type 0: normal (<25 intraepithelial lymphocytes per 100 enterocytes).; Type 1: increased intraepithelial lymphocytes but no villous atrophy (>25 intraepithelial lymphocytes per 100 enterocytes).; Type 2: villi still present but shortened.; Type 3: complete villous atrophy.	3 years