Adherence of a 1.600 mg Single Tablet 5-ASA Treatment of Ulcerative Colitis

Study Overview
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Brief Summary
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Several oral mesalazine (5-ASA) formulations exist, but the regimes require several tablets per day. Such regimens are not ideal and can interfere with normal daily activities of patients. Non-adherence has been associated with an increase in the risk of relapse and worse disease course; leading to a decrease in quality of life, an increase in societal and personal costs, and worst case increases the risk of colorectal cancer. Recently, a new formula for 5-ASA has been approved by the Danish Medicine Agency, with a single tablet regime per day. Primary purpose: • To investigate whether a simplified treatment regimen for 5- ASA (1600 mg as one tablet per day [intervention]) improves adherence with preserved remission rates compared to conventional therapy. Secondary purposes: Compare levels of endoscopic, mucosal and histological inflammation in predicting risk of relapse between the intervention group and the conventional therapy group. Investigate whether a simplified treatment regimen improves the disease course compared to the conventional therapy. To assess the correlation between different endpoints and the disease courses, with the use of clinical, endoscopic, histological, self-reported and biochemical markers. Improve, correlate and assess patient-reported outcomes in a prospective manner. To establish a biobank of cases with quiescent/mild ulcerative colitis (UC) for identification of future biomarkers.

Official Title
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Adherence of a 1.600 mg Single Tablet 5-ASA Treatment of Ulcerative Colitis (EASI-trial)

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Mesalazine
* Drug: Mesalazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Age between and including 18 and 60 Diagnosed with UC according to the Copenhagen Diagnostic Criteria Length of disease of max. 10 years Stable remission on 5-ASA (defined as partial Mayo score ≤1) for at least 2 months without need for oral corticosteroids before inclusion. Endoscopic remission defined as Mayo Clinic Endoscopic Score < 2 Have had a relapse within the last 2 years Defined as the need of escalation of treatment or change medical treatment. Exclusion Criteria: Evidence of infectious diarrhoea (i.e. pathogenic viruses, bacteria or Clostridium difficile toxin in stool culture) within the last month On immunomodulators, including methotrexate On any biological therapy Any previous abdominal surgery related to UC Any chronic infections (e.g. HBV, HCV, HIV) Any severe concomitant cardiovascular, autoimmune, hematologic, hepatic, renal, endocrine, oncologic or psychiatric disorder, which in the opinion of the investigator might have an influence on the patient's compliance or the interpretation of the results Well-founded doubt about the patient's cooperation, e.g., because of addiction to alcohol or drugs in the opinion of the investigators. Participation in another clinical trial within the last 30 days, or simultaneous participation in another clinical trial. Any previous documented allergic reaction to tested the medical drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1600 mg Asacol (mesalazine)<br>1600 mg mesalazine (Asacol) treatment regimen (1 tablet per day) for a year | Drug: Mesalazine<br>* 1600 mg Asacol [mesalazine]<br>|
| Active Comparator: 800 mg Asacol (mesalazine)<br>800 mg mesalazine (Asacol) treatment regimen (3 tablets per day) for a year | Drug: Mesalazine<br>* 800 mg Asacol [mesalazine]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medical Adherence | Measured by drug accountability log Patients having taken ≥80 % are categorised as adherent | through study completion, an average of 2 year | 
| Medical Adherence | Measured by Medical adherence rating scale (MARS) Medical adherence rating scale is a self-reported medical adherence tool consisting of 5 items scored on a 5 point Likert scale (ranging from 5-25). The scale has been used in several IBD studies and a global score > 20 indicates a good adherence. | through study completion, an average of 2 year | 
| Medical Adherence | Measured byf drug accountability log (outcome 1) and Medical adherence rating scale (MARS, outcome 2) separately, excl. pregnant and breastfeeding women. Further detail see outcome 1 and 2 | through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of disease activity by Mayo Score | The Mayo Score is composed of 4 items. A score from 0-2 is categorised as remission and 11-12 as severe. | through study completion, an average of 2 year | 
| Assessment of disease activity by the Simple clinical colitis activity index (SCCAI) | The SCCAI rely solely on clinical assessments. Clinical remission are defined as SCCAI < 1 and clinical response as a change of at least 1 point. | through study completion, an average of 2 year | 
| Assessment of endoscopic severity by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) | The UCEIS endoscopic severity on a scale of 1-4. Higher score mean worse disease severity. | through study completion, an average of 2 year | 
| Assessment of endoscopic severity by the Mayo endoscopic score | The Mayo endoscopic score is scored on a scale of 0-3. Higher score mean worse disease severity. | through study completion, an average of 2 year | 
| Assessment of histological severity by the Geboes score | The Geboes score is interpreted as such: a higher score means higher disease activity. | through study completion, an average of 2 year | 
| Assessment of histological severity by the Nancy Index | The Nancy Index are interpreted as such: The grade 4 correspond to severe disease, grade 0 as  absence of significant histological disease. | through study completion, an average of 2 year | 
| Assessment of histological severity by the Robarts Histopathology Index (RHI) | The RHI are interpreted as such: The score are ranging between 0 (no disease activity) to 33 (severe disease activity). | through study completion, an average of 2 year | 
| Correlation between the different clinical scores | Comparison, correlation and association between the different endoscopic, histological and disease activity indices. Included will be: Mayo score, Simple clinical colitis activity index (SCCAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Nancy Index, Robarts Histopathology Index (RHI) and the Geboes score (see outcome 4-10). | through study completion, an average of 2 year | 
| Remission - days | Differences in number of days in remission during the trial | through study completion, an average of 2 year | 
| Relapse - days | Differences in number of days in relapse during the trial | through study completion, an average of 2 year | 
| Remission and relapse - episodes | Differences episodes of relapses during the trial | through study completion, an average of 2 year | 
| Changes in quality of life | Prospective analyses of quality of life using 12-Item Short Form Survey (SF12). The SF12 is measured on a global score from 12-56. Beside a global score, a mental and physical dimension will also be calculated. | through study completion, an average of 2 year | 
| Changes in disease specific quality of life | Prospective analyses quality of life using the Short inflammatory bowel disease questionnaire (SIBDQ) The SIBDQ is a quality of life (QOL) questionnaire ranging from 10-70. Higher score means better QOL. | through study completion, an average of 2 year | 
| Changes in disability among ulcerative colitis patients | Prospective analyses of disability using the Inflammatory bowel disease disability index (IBD-DI) The IBD-DI measures the disability among patients with inflammatory bowel disease. Higher scores means worse disability. | through study completion, an average of 2 year | 
| Changes in sleep quality | Prospective analyses of sleep using the Pittsburgh Sleep Quality Index (PSQI), The PSQI was designed to measure sleep quality and disturbance. A global score > 5 is considered poor sleep quality. | through study completion, an average of 2 year | 
| Changes in resilience | Prospective analyses of resilience using the Brief Resilience Scale (BRS) The BRS is designed to measure the ability to bounce back or recover from stressful events. Higher scores means higher resilience. | through study completion, an average of 2 year |