Individualization Treatment Through a Self-managed Web-based Solution in Ulcerative Colitis

Individualization of Oral Mesalazine Treatment Through a Self-managed Web-based Solution in Mild-to-moderate Ulcerative Colitis: A Pilot Study

This study investigates the effect of individualized monotherapy with Mesalazine (Pentasa Sachet ®) on time to remission in patients with mild to moderate UC in an eHealth setting.

Study Overview

• Status: Terminated
• Conditions: Inflammatory Bowel Diseases; Ulcerative Colitis

Detailed Description

More than 3 million Europeans suffer from inflammatory bowel disease (IBD), where Crohn's Disease (CD) and Ulcerative Colitis (UC) are the most common forms. They are chronic, relapsing and remitting diseases resulting in uncontrolled inflammation of the gastrointestinal (GI) tract with symptoms of diarrhoea, abdominal pain, weight loss and blood in the stools. The treatment aims to relieve and prevent GI tract inflammation and consists of anti-inflammatory and immunosuppressive drugs or surgical removal of the colon as a final option. The main treatment option for mild to moderate UC is Aminosalicylate. Mesalazine (5-aminosalicylic acid), both orally and topically, has been proven to be an effective treatment option for inducing as well as maintaining remission in patients with UC.

Pentasa Sachet are Mesalazine micro granules coated in ethyl cellulose with high (95%) 5-aminosalicylic acid (5-ASA) load. The coating provides a prolonged release of Mesalazine, allowing a continuous action from small bowel to rectum. Approximately 75% of the micro granules are released in the colon. This reduces the number of applications needed per day and is therefore considered to be a more desirable option by the patients. Once daily administrated 5-aminosalicylic acid (5-ASA) has been shown to be as effective as conventional dosing.

Fecal Calprotectin (FC) is an accurate biomarker of GI tract inflammation. FC correlates well with endoscopic disease activity and consequently serves as a substitute marker for mucosal healing as well as a clinical tool for disease monitoring. A home testing kit with a smart phone application, which only takes 18 min to carry out, has been developed. Thereby, facilitating the opportunity of telemonitoring of the disease course and stimulating patient engagement, empowerment and adherence to treatment.

Medication adherence is essential for maintaining remission, since non-adherence is one of the main causes of disease activity. A combined therapy of oral and topical 5-ASA is recommended by current guidelines for the treatment of active mild to moderate UC. However, patient adherence to oral 5-ASA is poor (approximately 60%), and even poorer to topical therapy (approximately 32%). A previous eHealth trial on individualized oral 5-ASA therapy reported higher adherence rates than previous studies on standard care. In addition, 90% of the study patients responded with remission on monotherapy and only 10% needed a combined therapy with topical treatment.

Web-based treating solutions (eHealth) have shown to optimize treatment effect in chronic diseases such as asthma, type 1 diabetes, and coagulation diseases. A web-based treatment solution for IBD patients, Constant-care, was in 1997 launched by Dr. Pia Munkholm. The web-program has since been proven to be an effective clinical tool, resulting in enhanced compliance, empowerment, improved quality of life and decreased relapse duration in IBD patients. Constant-Care consists of an education package and a disease-monitoring package. The disease monitoring part of the program is built upon an algorithm of two variables; FC and a validated disease activity questionnaire, Simple Clinical Colitis Activity Index (SCCAI) for UC patients. The FC values are acquired by the patients through a home testing kit and the disease activity questionnaire is filled out by the patients in the web- program. The eHealth system cumulates the data immediately, and subsequently presenting the result, a Total inflammatory Burden Score (TIBS), to the patients as a visual "traffic light" indicator of disease activity. Patients receive treatment advices by the program depending on the severity of the disease: green- remission, yellow- moderate activity, red-severe activity.

The disease monitoring part also consists of Patient-Related Outcome (PRO) questionnaires regarding quality of life, disability, fatigue, disease course type and compliance. The International Organization for the study of Inflammatory Bowel Disease (IOIBD) has since 2015 recommended the use of PRO's as a fundamental part of measuring treatment outcome in both UC and CD.

The primary aim of the study is to investigate the effect of individualized monotherapy with Mesalazine (Pentasa Sachet ®) on time to remission (clinical and Paraclinical (green TIBS)) in patients with mild to moderate UC in an eHealth setting. The investigators hypothesize that the web based therapy program will reduce the time to remission compared to standard care.

• Study Type: Observational
• Enrollment (Actual): 1

Contacts and Locations

Study Locations

• Denmark
  • Frederikssund, Denmark, 3600
    • North Zealand University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

20 patients with mild to moderate ulcerative colitis will be included from the Out patient clinic at the gastroenterology department, North Zealand University Hospital, Capitol region of Denmark

Description

Inclusion Criteria:

• Fulfil the Copenhagen Diagnostic criteria for UC
• Age between 18 and 75 years
• New and relapse patients diagnosed with Mild-to-moderate UC
• Current relapse (minimum 1 out of 2) SCCAI>2 (with a positive score in the variable of blood in stool) FC ≥200
• Diagnosed with left sided or extensive UC(24)
• Understand written and spoken Danish
• Easy access to internet and smartphone

Exclusion Criteria:

• Evidence of enteric infection
• Treatment with immunomodulators such as steroids, azathioprine, methotrexate, or infliximab within the last 8 weeks
• Two or more courses of oral steroids in the past 12 months
• Diagnosed with proctitis
• Severe disease activity (SCCAI >6 or FC ≥600)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Inflammation Burden Scoring (TIBS)	Self reported disease activity in combination with a fecal biomarker of inflammation (fecal calprotectin) results in TIBS. Disease activity is scored by 6 questions yielding: remission (<3) , mild to moderate disease activity (3-4) and severe disease activity ( >5). Fecal calprotectin: remission (<200mg/kg ), mild to moderate (200-599 mg/kg ), severe (>599 mg/kg). The two items are added together in a weighted manner giving the Total inflammation burden scoring (TIBS): remission (0-8), mild to moderate (9-32), severe (33-99).	At baseline and at 12 weeks or until remission, which ever comes first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease course type	Self reported Disease course type according to the Copenhagen disease course type ( 5 different types). The five disease course types stretch from mild and indolent to constant active disease. In this study, patients have to choose one type representing their disease course since time of diagnosis, as well as at week 12 for the period since inclusion in the study.	At baseline and after 12 weeks
Compliance with medication	self reported according to the Medicine Adherence Report Scale and visibility analog scale. Compliance scored according to Medicine Adherence Report Scale by 5 questions, and 1-5 points per question ( 5 = always, 1=never), maximum score 25. A score over 20 is considered god compliance. Visibility analog scale from 0-100, where 0 means no compliance and 100 means 100% compliant.	at baseline and after 12 weeks
Short Inflammatory Bowel Disease Questionnaire	self reported quality of life according to the Short Inflammatory Bowel Disease Questionnaire, a disease specific health related quality of life questionnaire consisting of 10 questions in four domains: Emotional Health, Bowel Symptoms, Social Health and Work. The scoring range is from 10 (lowest score) to 70 (highest score). A cut-off level at >50 is interpreted as good health related quality of life.	at baseline and after 12 weeks
Disability	self reported disability according to the IBD disk, consisting of 10 items: Abdominal pain, regulating defecation, interpersonal interactions, education and work, Sleep, energy, emotions, body image, sexual functions, joint pain. Patients can score from 0 (absolutely disagree/ no disability) to 10 (absolutely agree/severe disability) for each item. The results will be visualised to the patient as a coloured disc.	at baseline and after 12 weeks
Fatigue	Fatigue is measured according to The Functional Assessment of Chronic Illness Therapy-Fatigue Scale, containing 13 questions to measure the fatigue component of health related quality of life. The scale ranges from 0-52 with zero being the worst possible score and 52 the best. A score of ≤30 represents fatigue	at baseline and after 12 weeks

Collaborators and Investigators

• Sponsor: Nordsjaellands Hospital
• Collaborators: Ferring Pharmaceuticals
• Investigators: Study Director: Pia Munkholm, Prof, North Zealand University Hospital

Publications and helpful links

General Publications

• Vinding KK, Elsberg H, Thorkilgaard T, Belard E, Pedersen N, Elkjaer M, Marker D, Carlsen K, Burisch J, Munkholm P. Fecal Calprotectin Measured By Patients at Home Using Smartphones--A New Clinical Tool in Monitoring Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis. 2016 Feb;22(2):336-44. doi: 10.1097/MIB.0000000000000619.
• Pedersen N, Thielsen P, Martinsen L, Bennedsen M, Haaber A, Langholz E, Vegh Z, Duricova D, Jess T, Bell S, Burisch J, Munkholm P. eHealth: individualization of mesalazine treatment through a self-managed web-based solution in mild-to-moderate ulcerative colitis. Inflamm Bowel Dis. 2014 Dec;20(12):2276-85. doi: 10.1097/MIB.0000000000000199.
• Elkjaer M, Shuhaibar M, Burisch J, Bailey Y, Scherfig H, Laugesen B, Avnstrom S, Langholz E, O'Morain C, Lynge E, Munkholm P. E-health empowers patients with ulcerative colitis: a randomised controlled trial of the web-guided 'Constant-care' approach. Gut. 2010 Dec;59(12):1652-61. doi: 10.1136/gut.2010.220160.
• Pedersen N, Elkjaer M, Duricova D, Burisch J, Dobrzanski C, Andersen NN, Jess T, Bendtsen F, Langholz E, Leotta S, Knudsen T, Thorsgaard N, Munkholm P. eHealth: individualisation of infliximab treatment and disease course via a self-managed web-based solution in Crohn's disease. Aliment Pharmacol Ther. 2012 Nov;36(9):840-9. doi: 10.1111/apt.12043.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2019
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Adherence; eHealth; Aminosalicylate
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Ulcer; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: H-17038710

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No