Crohn DiseaseCROHNLYNCT05874349
Histopathologic and Lymphocyte Subpopulations Evaluation of the Upper Gastrointestinal Tract of Crohn's Disease
An observational study of Crohn Disease, run by Hospital Mutua de Terrassa at 1 site in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- General variables, Clinical activity and Laboratory data
- Type of treatment
- Surgery or procedure, Lifestyle or therapy programme
- How many people
- 200 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jun 2017to 1 Jan 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The definition of the study population was patients with CD diagnosed according to the criteria of the ECCO guidelines. The definition of control populations was patients with celiac disease diagnosed according to the Catassi and Fasano criteria and control subjects.
Who may be able to join
- 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)
Who cannot join
- Refusal of the patient to participate in the study
- Pregnancy
- Serious comorbidities: heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Histopathologic and Lymphocyte Subpopulations Evaluation of the Upper Gastrointestinal Tract of Crohn's Disease: A Multicentre Prospective Study (CROHNLY Project)
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.
Read more
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.
Read the detailed 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.
- Conditions
- Crohn Disease
- Being tested
- General variables, Clinical activity, Laboratory data, Endoscopic and histology data
- Keywords
- Crohn Disease
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
General variablesBehavioural
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 activityBehavioural
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).
Laboratory dataProcedure or surgery
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 dataProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Crohn's disease | Patients with CD diagnosed according to the criteria of the ECCO guidelines. For the histological and lymphocyte subpopulation analysis of duodenal samples, all patients with CD who required an endoscopic examination during the disease have been prospectively included. All the recorded variables were registered at the moment of the endoscopy. Receives: Behavioral: General variables; Behavioral: Clinical activity; Procedure: Laboratory data; Procedure: Endoscopic and histology data | |
| Cohort 2: Control groups | Two groups are included: 1) Disease control: Patients with celiac disease diagnosed according to the Catassi and Fasano criteria and 2) Healthy control subjects. For the histological and lymphocyte subpopulation analysis of duodenal samples, patients with celiac disease were prospectively included to undergone gastroscopy, before starting gluten-free diet. Control subjects were patients referred for upper endoscopy due to digestive symptoms that have normal appearing mucosa both at endoscopic and histological assessment (Marsh 0, <25 intraepithelial lymphocytes). Serological markers of celiac disease were negative and they have no signs of inflammatory bowel diseases. Receives: Behavioral: General variables; Behavioral: Clinical activity; Procedure: Laboratory data; Procedure: Endoscopic and histology data |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (2)
Percentage of lymphocyte subpopulations in the duodenum of patients with CD.
Percentage of lymphocyte subpopulations are assessed by flow cytometry.
Measured: 3 years
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2023
- Study start1 Jun 2017
- Primary completion1 Jun 2020
- Study completion1 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn 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
- Prospective
- Enrolment
- 200 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
- NCT05874349
- Sponsor's protocol ID
- CROHNLY23
- Acronym
- CROHNLY
- Status last verified
- May 2023
- First submitted
- 12 Apr 2023
- Last updated
- 24 May 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 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Histopathologic and Lymphocyte Subpopulations Evaluation of the Upper Gastrointestinal Tract of Crohn's Disease: A Multicentre Prospective Study (CROHNLY Project)
- ClinicalTrials.gov ID
- NCT05874349
- Acronym / sponsor ID
- CROHNLY / CROHNLY23
- Conditions
- Crohn Disease
- Keywords
- Crohn Disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Hospital Mutua de TerrassaUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jan 2023 (actual)
- First posted
- 24 May 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.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Crohn's disease | – | Behavioral: General variables, Behavioral: Clinical activity, Procedure: Laboratory data, Procedure: Endoscopic and histology dataPatients with CD diagnosed according to the criteria of the ECCO guidelines. For the histological and lymphocyte subpopulation analysis of duodenal samples, all patients with CD who required an endoscopic examination during the disease have been prospectively included. All the recorded variables were registered at the moment of the endoscopy. |
| Cohort 2: Control groups | – | Behavioral: General variables, Behavioral: Clinical activity, Procedure: Laboratory data, Procedure: Endoscopic and histology dataTwo groups are included: 1) Disease control: Patients with celiac disease diagnosed according to the Catassi and Fasano criteria and 2) Healthy control subjects. For the histological and lymphocyte subpopulation analysis of duodenal samples, patients with celiac disease were prospectively included to undergone gastroscopy, before starting gluten-free diet. Control subjects were patients referred for upper endoscopy due to digestive symptoms that have normal appearing mucosa both at endoscopic and histological assessment (Marsh 0, <25 intraepithelial lymphocytes). Serological markers of celiac disease were negative and they have no signs of inflammatory bowel diseases. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The definition of the study population was patients with CD diagnosed according to the criteria of the ECCO guidelines. The definition of control populations was patients with celiac disease diagnosed according to the Catassi and Fasano criteria and control subjects.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (3 listed)
- Refusal of the patient to participate in the study
- Pregnancy
- Serious comorbidities: heart disease, chronic obstructive pulmonary disease, liver disease, bleeding disorders, etc
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 |
|---|---|---|
| General variablesVariables 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, ...). | Behavioural | Cohort 1: Crohn's disease, Cohort 2: Control groups |
| Clinical activityClinical 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). | Behavioural | Cohort 1: Crohn's disease, Cohort 2: Control groups |
| Laboratory dataLaboratory 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. | Procedure or surgery | Cohort 1: Crohn's disease, Cohort 2: Control groups |
| Endoscopic and histology dataEndoscopic 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. | Procedure or surgery | Cohort 1: Crohn's disease, Cohort 2: Control groups |
Primary outcome
Description of microscopic lesions in the upper digestive tract in patients with CD.
Time frame: 3 years
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.
2 secondary outcomes
Percentage of lymphocyte subpopulations in the duodenum of patients with CD.
Time frame: 3 years
Description of "sprue-like" enteropathy associated with the use of immunosuppressants in CD.
Time frame: 3 years
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 24 May 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 Crohn 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 5 inclusion and 3 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 24 May 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?
Description of microscopic lesions in the upper digestive tract in patients with CD. (time frame: 3 years). 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 24 May 2023.