Gelsectan® in the Treatment of Patients With Diarrhoea-predominant Irritable Bowel Syndrome
- Conditions
- Irritable Bowel Syndrome (IBS)Irritable Bowel Syndrome of Diarrhea Type (IBS-D)
- Interventions
- Device: Gelsectan®Drug: Placebo
- Registration Number
- NCT06681012
- Lead Sponsor
- Devintec Sagl
- Brief Summary
Irritable Bowel Syndrome (IBS) is one of the major Disorders of Gut-Brain Interaction (DGBI) and the most frequent reasons for referral to both primary care providers and gastroenterologists.IBS is not a life-threatening disease, but imposes a significant burden on society, entailing a decrease in patients' Quality of Life (QoL), elevated rates of psychological comorbidities and loss of work productivity, which might be the greatest in subjects with IBS-D, for whom the fear of incontinence in a social situation can be especially debilitating. Moreover, IBS is associated with significant direct and indirect healthcare costs and has a considerable socioeconomic impact on society.
Treatment strategy for IBS is usually based on predominant symptoms and their severity, and requires a strong patient-physician relationship, as well as both non-pharmacological and pharmacological approaches. Lifestyle interventions, such as dietary modifications, physical activity and lifestyle adjustments, and stress reduction/psychological therapy represent the most important initial non-pharmacological clinical approach for IBS patients, especially for those with mild disease. First-line pharmacological options for IBS-D include antidiarrheals, mainly loperamide, to control diarrhoea, as well as antispasmodic drugs to relieve IBS symptoms, in particular abdominal pain. Second-line therapies indicated for the treatment of global IBS-D symptoms include rifaximin, 5-Hydroxytryptamine (5-HT)3 receptor antagonists (alosetron, ondansetron and ramosetron) and eluxadoline. Other treatments recommended in patients with IBS-D consist of Tricyclic Anti-Depressants (TCAs) and bile acid sequestrants.
Notably, management of patients with IBS is challenging since diagnosis and treatment could require several therapeutical strategies with often partial and unsatisfactory results. Indeed, most patients with IBS are dissatisfied with their current therapy and 34% report no symptom control, according to the IBS Global Impact Report of 2018.
At present, there is a growing interest in therapeutic approaches for IBS-D aimed at improving intestinal barrier integrity for a more efficient control of symptoms, considering that an intestinal epithelial barrier dysfunction and mucosal immune activation have been suggested as a central mechanism in IBS-D pathophysiology. In this perspective, film-forming agents capable of protecting the intestinal mucosal barrier, such as Xyloglucan (XG) and Pea protein may represent a valid alternative therapeutic option for the management of IBS-D.
Gelsectan® is a CE-marked medical device under the European Union (EU) Medical Device Regulation (MDR) 2017/745, whose classification under the MDR is class III. Gelsectan® contains XG, Pea protein, grape seed extract, and Xylo-Oligosaccharides (XOS) and is indicated for symptomatic relief and prevention of chronic or relapsing diarrhoea, abdominal tension, pain, bloating and flatulence, as well as protection and restoration of intestinal mucosal function. Based on previous non-clinical studies and two clinical investigations, Gelsectan® seems to be safe and exert a protective action on the intestinal mucosa, mediating the restoration of intestinal permeability and the improvement of gastrointestinal symptoms associated with IBS-D. In particular, a 28-day treatment with Gelsectan® significantly reduced IBS-D-associated diarrhoea, abdominal pain and bloating, with no related adverse events in a randomized, placebo-controlled, cross-over clinical study. Moreover, Gelsectan® treatment for 6 months was generally safe and effective in improving IBS severity, diarrhoea and bowel habit, as well as pain and bloating, in a recent multicentre, open-label, prospective, observational study. Of note, Gelsectan® was also mentioned in the recent clinical practice guidelines on IBS-D and functional diarrhoea of the United European Gastroenterology (UEG) and the European Society for Neurogastroenterology and Motility (ESNM), and a recent consensus on IBS conducted by a panel of Belgian gastroenterologists.
With these premises, the present study aims to further assess the performance and safety of Gelsectan® within the scope of its intended purpose, compared with placebo, on overall abdominal pain and symptoms in patients with IBS-D in a randomized, double-blind, parallel-group clinical study.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 330
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Gelsectan® Gelsectan® Gelsectan® is a class III CE-marked medical device under the Regulation (EU) 2017/745 (MDR), which has been present on the EU market since 2017. Gelsectan® medical device consists of non-sterile capsules containing film-forming compounds (Xyloglucan, Pea protein, grape seed extract, and Xylo-oligosaccharide) indicated for symptomatic relief and prevention of IBS symptoms. Placebo Placebo Placebo capsule, comparable in size, appearance and taste, packaging and labelling, as well as mode and schedule of administration to the IMD (i.e., Gelsectan®).
- Primary Outcome Measures
Name Time Method Effect of Gelsectan® on the composite response rate for abdominal pain and stool consistency over the 8-week treatment period, at the end of treatment, in patients with IBS-D, according to Rome IV criteria. From enrollment to the end of treatment at 8 weeks Proportion of composite responders over 8 weeks determined at the End of Treatment.
A composite responder is defined as a patient who meet the following criteria for at least 50% of the 8-week treatment period:
* Pain response criteria: reduction of at least 30% in the weekly average score of the 24-hour worst abdominal pain compared with baseline, measured with the 11-point Numeric Rating Scale (from 0=none to 10=worst possible pain) AND
* Stool consistency response criteria: reduction of at least 50% in the number of days per week with at least one stool that has a consistency of BSFS types 6 or 7 compared with baseline, measured daily using the Bristol Stool Form Scale - BSFS (from 1=separate hard lumps, like nuts to 7=watery, no solid pieces).
A patient needs to fulfil both aforementioned response criteria for abdominal pain and stool consistency in the same week to be considered a responder for that week.
- Secondary Outcome Measures
Name Time Method Effect of Gelsectan® on overall IBS-D symptoms: composite response rate for abdominal pain and stool consistency over 4-week intervals From enrollment to the end of treatment at 8 weeks and each 4-week interval, as well as the 4-week post-treatment period Proportion of composite responders over each 4-week intervals.
A composite responder is defined as a patient who meet the following criteria for at least 50% of the 8-week treatment period:
* Pain response criteria: reduction of at least 30% in the weekly average score of the 24-hour worst abdominal pain compared with baseline, measured with the 11-point Numeric Rating Scale (from 0=none to 10=worst possible pain) AND
* Stool consistency response criteria: reduction of at least 50% in the number of days per week with at least one stool that has a consistency of BSFS types 6 or 7 compared with baseline, measured daily using the Bristol Stool Form Scale - BSFS (from 1=separate hard lumps, like nuts to 7=watery, no solid pieces).
A patient needs to fulfil both aforementioned response criteria for abdominal pain and stool consistency in the same week to be considered a responder for that week.Effect of Gelsectan® on overall IBS-D symptoms: Proportion of pain responders From enrollment to the end of treatment at 8 weeks and each 4-week interval, as well as the 4-week post-treatment period Proportion of pain responders, defined as patients who meet the pain response criteria (i.e., reduction of at least 30% in the weekly average score of the 24-hour worst abdominal pain compared with baseline) for at least 50% of the observation period.
The standard 11-point Numeric Rating Scale (NRS-11) (from 0=none to 10=worst possible pain imaginable) will be used for the measure of pain.Effect of Gelsectan® on overall IBS-D symptoms: Proportion of stool consistency responders From enrollment to the end of treatment at 8 weeks and each 4-week interval, as well as the 4-week post-treatment period Proportion of stool consistency responders, defined as patients who meet the stool consistency response criteria (i.e., reduction of at least 50% in the number of days per week with at least one stool that has a consistency of BSFS types 6 or 7 compared with baseline) for at least 50% of the observation period.
Stool consistency will be measured daily using the Bristol Stool Form Scale - BSFS (from 1=separate hard lumps, like nuts to 7=watery, no solid pieces).Effect of Gelsectan® on overall IBS-D symptoms: Mean 24-hour worst abdominal pain score From enrollment to the end of the 12 weeks study period Mean 24-hour worst abdominal pain score, as self-assessed by patients daily up to Week 12 using the Numeric Rating Scale (NRS-11) (from 0=none to 10=worst possible pain imaginable)
Effect of Gelsectan® on overall IBS-D symptoms: Mean stool type From enrollment to the end of the 12 weeks study period Mean number of days/week with a BSFS type ≤ 2, ≥ 3 and ≤ 5, and ≥ 6, as well as changes from baseline, as self-assessed by patients daily up to Week 12 through the Bristol Stool Form Scale - BSFS (from 1=separate hard lumps, like nuts to 7=watery, no solid pieces).
Effect of Gelsectan® on overall IBS-D symptoms: Mean number of stools/day From enrollment to the end of the 12 weeks study period Mean number of stools/day (average daily frequency of defecation)
Effect of Gelsectan® on overall IBS-D symptoms: Mean weekly average score for bloating From enrollment to the end of the 12 weeks study period Mean weekly average score for bloating, as self-assessed by patients using a 7-point Likert scale (ranging from 0 to 6, where 0= not bad/bothersome at all and 6= extremely bad/bothersome)
Effect of Gelsectan® on overall IBS-D symptoms: Mean weekly average score for urgency of defecation From enrollment to the end of the 12 weeks study period Mean weekly average score for urgency of defecation, as self-assessed by patients weekly using a 7-point Likert scale (ranging from 0 to 6, where 0= no urgency at all and 6= a very great deal of urgency)
Effect of Gelsectan® on IBS symptom severity: Proportion of patients with global improvement of IBS From enrollment to the end of treatment at 8 weeks and after 4-week post-treatment period Proportion of patients with global improvement of IBS, defined as a score of at least 4 on the IBS Global Assessment of Improvement (IBS-GAI).
IBS-GAI score ranging from 0 to 6 (where 0 = "substantially worse", 1 = "moderately worse", 2 = "slightly worse", 3 = "unchanged", 4 = "slightly improved", 5 = "moderately improved", and 6 = "substantially improved").Effect of Gelsectan® on IBS symptom severity measured by the IBS-Symptom Severity Scale score From enrollment to the end of treatment at 8 weeks and after 4-week post-treatment period Change from baseline in IBS severity, as measured by the IBS-Symptom Severity Scale (IBS-SSS) score.
IBS-SSS is a validated five-item questionnaire measuring the frequency and intensity of abdominal pain, the severity of abdominal distension, the dissatisfaction with bowel habits, and the interference of IBS with daily life. Each item is rated from 0 to 100, with a total score ranging from 0 to 500, with higher scores indicating a greater severity. Severity of IBS can be graded as mild (\<175), moderate (175-300), or severe (\>300) based on the IBS-SSS total score.Effect of Gelsectan® on work productivity and activity impairment due to IBS From enrollment to the end of the 12 weeks study period Change from baseline of work productivity and activity impairment due to IBS, as measured by the Work Productivity and Activity Impairment (WPAI):IBS questionnaire scores.
WPAI:IBS is a validated questionnaire consisting of six items intended to assess work productivity and daily activity impairment due to IBS in the preceding 7 days (Visual Analogue Scale \[VAS\] from 0 to 10) and daily activity impairment resulting from IBS (VAS from 0 to 10).
WPAI:IBS scores are represented as percentages (range of 0-100%), with higher percentages indicating a greater work productivity loss and daily activity impairment.Effect of Gelsectan® on quality of life as measured by World Health Organization Quality of Life Brief Version (WHOQOL-BREF) From enrollment to the end of the 12 weeks study period Change from baseline of patient QoL, as measured by World Health Organization Quality of Life Brief Version (WHOQOL-BREF).
The WHOQOL-BREF questionnaire is a validated measurement of QoL consisting of an abbreviated, 26-item version of the 100-item WHOQOL-100 QoL measure. The WHOQOL-BREF addresses four QoL domains, i.e., physical health (7 items), psychological health (6 items), social relationships (3 items) and environment (8 items), with each item graded on a 5-point Likert scale. Each domain score is calculated by multiplying by a factor of four the mean of all item scores. Domain scores are then transformed to a 0-100 scale, with higher scores indicating a better QoL.Effect of Gelsectan® on depression symptoms From enrollment to the end of the 12 weeks study period Change from baseline of symptoms of depression, as measured by the Patient Health Questionnaire (PHQ)-9 score.
PHQ-9 is a nine-item questionnaire assessing depression symptoms according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) in the past two weeks, with each item score ranging from 0 (not at all) to 3 (nearly every day). The PHQ-9 total score is representative of depression severity and ranges from 0 to 27, by which depression is defined as mild (5-9), moderate (10-14), moderate (15-19) or severe (more than 20).Use of rescue therapy From enrollment to the end of treatment at 8 weeks Use of rescue therapy (type and posology) during treatment
Healthcare utilization From enrollment to the end of treatment at 8 weeks Incidence of visits to patient's General Practitioner (GP), Emergency Room (ER) visits and unplanned hospitalizations (with length of stay)
Safety: adverse events and device deficiencies From enrollment to the end of treatment at 8 weeks Incidence and type of all adverse events and device deficiencies throughout the study
Safety: changes in systolic and diastolic Blood Pressure From enrollment to the end of treatment at 8 weeks Changes in systolic and diastolic Blood Pressure (mmHG)
Safety: changes in Heart Rate From enrollment to the end of treatment at 8 weeks Changes in Heart Rate (bpm)
Safety: Changes in Respiratory Rate From enrollment to the end of treatment at 8 weeks Changes in Respiratory Rate (breaths per minute)
Safety: Changes in the concentration of Glucose, Blood Urea Nitrogen (BUN), bilirubin, creatinine From enrollment to the end of treatment at 8 weeks Changes in the concentration of Glucose, Blood Urea Nitrogen (BUN), bilirubin, creatinine (mg/dl)
Safety: Changes in the concentration of Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase From enrollment to the end of treatment at 8 weeks Changes in the concentration of Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase (U/L)
Safety: Changes in White Blood Cell count, Platelet count, Red Blood Cell count From enrollment to the end of treatment at 8 weeks Changes in White Blood Cell count, Platelet count, Red Blood Cell count
Safety: Changes in haemoglobin concentration From enrollment to the end of treatment at 8 weeks Changes in haemoglobin (g/dl) concentration
Safety: Changes in haematocrit From enrollment to the end of treatment at 8 weeks Changes in haematocrit (%)
Safety: changes in urine specific gravity From enrollment to the end of treatment at 8 weeks Changes in urine specific gravity
Safety: changes in urine pH From enrollment to the end of treatment at 8 weeks Changes in urine pH
Safety: changes in urine protein, glucose, bilirubin, ketones, blood concentrations From enrollment to the end of treatment at 8 weeks Changes in urine protein, glucose, bilirubin, ketones, blood concentrations (mg/dl)
Trial Locations
- Locations (8)
IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola
🇮🇹Bologna, BO, Italy
IRCCS Ca' Granda Ospedale Maggiore Policlinico Foundation
🇮🇹Milano, Italy
AOU Federico II di Napoli
🇮🇹Napoli, Italy
Azienda Ospedale Università Padova
🇮🇹Padova, Italy
Azienda Ospedaliero Universitaria Pisana (AOUP)
🇮🇹Pisa, Italy
S. Andrea University Hospital
🇮🇹Roma, Italy
Hospital Universitario Vall d´Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain