Clinical trial NCT06031064: External Validation of a Microscopic Colitis Clinical Scoring System in Patients With Chronic Watery Diarrhoea
Official title: External Validation of a Clinical Scoring System to Predict Microscopic Colitis in Patients With Chronic Watery Diarrhoea
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Microscopic Colitis
Keywords: Inflammatory bowel disease (IBD)
clinical scoring
chronic watery diarrhea
Lead sponsor: Hospital Mutua de Terrassa
Sponsor class: OTHER
First posted: 2023-09-11
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients derived at the digestive system department with chronic watery diarrhoea and clinical suspicion of MC, requiring colonoscopy with biopsies to complete the study

Brief summary: Chronic watery diarrhoea is a very common problem in the population and most of these patients will be referred for colonoscopy. If no macroscopic findings are observed during colonoscopy to justify the diarrhoea, serial colonic biopsies will be taken to rule out Microscopic Colitis (MC). However, it has been estimated that only 10-15% of these patients will be diagnosed with MC after colonoscopy. Therefore, about 80% of the biopsies collected and analysed will not be useful to establish a diagnosis, considerably increasing costs.

To predict the risk of developing MC, a new promising clinical scoring system has been recently developed. This score will be useful in the diagnostic work-up of chronic watery diarrhoea to prioritize colonoscopy with stepwise colonic biopsies in patients with a positive highly specific score for MC. In cases with a negative score, colonoscopy plus biopsies should be performed only if other diagnostic tests are negative.

The aim of this current study is to externally validate the new scoring system to predict MC in patients with chronic watery diarrhoea.

Detailed description: Two diagnostic scoring systems have been proposed to predict the risk of developing MC: 1) The Kane score (sensitivity (SN) 96%; specificity (SP) 46%) combines eight risk factors, including female sex, age over 50 years, weight loss, absence of abdominal pain, and use of proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs), presence of nocturnal diarrhoea and diarrhoea duration of less than 6 months. 2) The Cotter score (SN 93%; SP 49%) includes age ≥55 years, duration of diarrhoea ≤6 months, ≥5 bowel movements per day, body mass index \<30 kg/m2, current smoking, and current use of selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and NSAIDs. However, both scoring systems have been derived from retrospective studies and watery chronic diarrhoea, the hallmark clinical symptom of MC, was not well defined.

Besides MC risk factors, faecal markers could also be useful for MC screening. Most studies have found that 60-75% of the patients with active collagenous colitis, a subtype of MC, have elevated faecal calprotectin levels. Moreover, a recent study showed that faecal calprotectin concentrations \>100 μg/g (AUC, 0.73) showed a 67% sensitivity and 75% specificity to predict MC.

To further assess the value of the Kane and Cotter scoring systems and to derive a new score including faecal calprotectin aiming to increase specificity, the investigators performed a prospective observational two-centres study. Chronic watery diarrhoea was defined as ≥2 watery stools (Bristol 6-7) per day, of frequent occurrence (≥3 times per week), of at least 1 month duration. A registry of demographic and clinical characteristics (VAS of 0-100 of abdominal pain and abdominal distension, presence of nocturnal diarrhoea, urgency and faecal incontinence, smoking, body mass index, weight loss, use of drugs) was performed. The study included 118 patients with chronic watery diarrhoea, from which 41 were diagnosed with MC (21 lymphocytic colitis, 16 collagenous colitis and 4 paucicellular colitis) and obtained lower SN and SP values than those published of the Cotter (SN 78%; SP 57%) and Kane (SN 78%; SP 38%) scores. The AUC of both scores was 0.71 and 0.66, respectively. The multivariate analysis identified 5 variables associated with MC: \>5 stools/day (OR 12.5), duration of diarrhoea ≤8 months (OR 5), regular use of low-dose acetylsalicylic acid (ASA) (OR 4), BMI ≤26 Kg/m2 (OR 4.1) and faecal calprotectin \>500 µg/g (OR 5.5). A new score was developed using the variables mentioned above with an AUC of 0.86 (p\<0.001 vs. Kane and Cotter scores). A score \>10 had a sensitivity of 61.5% and a specificity of 92%. A score \>17 gave a specificity of 100% with a sensitivity of 36%. The score was internally validated using bootstrapping techniques.

Although promising, the new scoring system must be externally validated before generalizing its use in clinical practice.

Eligibility criteria: Inclusion Criteria:

* Age 40 years or older.
* Patient with chronic non-bloody watery diarrhoea (Bristol scale=6 or 7), with 2 or more liquid stools per day, of frequent occurrence (at least 3 times per week), of at least 1 month's duration.
* Normal blood test and biochemistry (including C reactive protein and TSH), negative anti-transglutaminase antibodies, and negative faecal ova and parasites. A 75SeHCAT is not mandatory.
* Patients with an indication for a diagnostic colonoscopy by their physician at charge, mainly to rule out MC.
* Signature of the study informed consent

Exclusion Criteria:

* Patients with either alternating diarrhoea-constipation or self-limiting diarrhoea at the time of colonoscopy.
* History of inflammatory bowel disease or coeliac disease, bile acid diarrhoea.
* Previous gastrointestinal surgery (excluding appendectomy or inguinal herniorrhaphy).
* Incomplete colonoscopy or no colon biopsies of at least right and left colon in separate containers (minimum 2 samples of each segment).
* Unsatisfactory preparation for a complete exploration (Boston scale \<6, any segment \<2)
* Significant macroscopic lesions on colonoscopy, other than those occasionally described in MC
* Inability to understand the instructions for participating in the study.

Primary outcomes:
measure: Percentage of patients diagnosed with Microscopic Colitis (MC)
timeFrame: up to 2 months (after clinical and histological assessment)
Secondary outcomes:
measure: Faecal calprotectin concentration (μg/g)
timeFrame: at inclusion (prior to colonoscopy)
Other outcomes:
Locations:
city: Terrassa
country: Spain
facility: Hospital Universitari MútuaTerrassa
state: Barcelona
Study officials:
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