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Goal of this study is to evaluate the efficacy and safety of two different doses of Linaclotide in improving bowel function and patient-reported outcomes among Bangladeshi patients with chronic constipation for 8 weeks along with an additional short drug-free follow up period of 2 weeks. The main question it aims to answer is "Does Linaclotide at doses of 72microgram or 145microgram once daily improve bowel function and patient-reported coutcomes compared with placebo in Bangladeshi patients with chronic constipation over an 8-week treatment period?"
Study procedure:
From outpatient department of Gastroenterology, Dhaka Medical College, a total of 90 adult patients diagnosed with chronic idiopathic constipation (CIC) or constipation predominant irritable bowel syndrome (IBS-C) by ROME-IV criteria will be selected after baseline evaluation including clinical history, physical examination, laboratory tests and colonoscopy. Before enrollment eligible participants will undergo 1-week baseline stool diary which will include baseline data of patient reported severity of abdominal symptoms (bowel movement, stool frequency, bloating, abdominal pain or discomfort and defecatory satisfaction score). Patients reporting more than 3 SBMs during baseline run in period will be excluded from the study. Finally total 90 patients will be enrolled as participants who will be randomly assigned to one of the three groups, Group A (Linaclotide 72mcg once daily), Group B (Linaclotide 145mcg once daily) and Group C (Placebo once daily ). The treatment period will start from randomization visit (day 0) and will be continued for 8 weeks. All participants will receive identical looking drugs (72mcg or 145mcg or placebo) 30 minutes before breakfast and they will be requested to maintain standard dietary and lifestyle advices including increased intake of high fiber diet and fluid throughout the study. Patients will record spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM), stool consistency using Bristol Stool Form Scale (BSFS), severity of abdominal symptoms by 5-point Likert scale, use of rescue medication after 3 days of absolute constipation and adverse events such as diarrhea in their daily stool diary. They will be followed up at week-4, week-8 and after 2-week drug free withdrawal period at week-10 with review of stool diary and safety assessments. Entire study will be monitored by Data Safety Monitoring Board (DSMB) of Dhaka Medical College.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Linaclotide 72 | Experimental | Group A - Linaclotide 72 mcg |
|
| Linaclotide 145 | Experimental | Group B - Linaclotide 145 mcg |
|
| Placebo | Placebo Comparator | Group C - Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Linaclotide 72 micrograms | Drug | Linaclotide 72 micrograms will be given in Group A |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Spontaneous Bowel Movement (CSBM) responder rate | Complete Spontaneous Bowel Movement (CSBM) responder rate is defined as the proportion of patients achieving 3 or more complete spontaneous bowel movements (CSBM) per week with an increase of 1 or more CSBM per week from baseline for at least 6 of the treatment weeks. Patient will be maintaining a daily stool diary from which data will be obtained and CSBM responder rate will be assessed. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change in weekly SBM frequency | Mean change in weekly Spontaneous Bowel Movement (SBM) after 8 weeks from baseline. | 8 weeks |
| Mean change in CSBM frequency | Mean change in weekly Complete Spontaneous Bowel Movement (CSBM) after 8 weeks from baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dr. Md Mehedi Shahriar, MBBS | Contact | +8801753085062 | msreehan85@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dhaka Medical College | Dhaka | Bangladesh |
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Phase IV investigator initiated trial with off-label dose evaluation
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| Linaclotide 145 micrograms |
| Drug |
Linaclotide 145 micrograms will be given in Group B |
|
| Placebo | Other | Placebo will be given in Group C |
|
| 8 weeks |
| Changes in weekly stool consistency measured by Bristol Stool Form Scale (BSFS) | Change in weekly stool consistency from baseline using Bristol Stool Form Scale (BSFS). The scale consists of various stool forms from type 1 to type 7. (Type 1- separate hard lumps, like nuts and hard to pass, Type 2-sausage shaped but lumpy, Type 3- Like a sausage but with cracks on the surface, Type 4- Like a sausage or snake, smooth and soft, Type 5- soft blobs with clear cut edges, Type 6- fluffy pieces ragged edges, a mushy stool, Type 7- watery, no solid pieces, entirely liquid). | 8 weeks |
| Change in average weekly bloating score | Change in average weekly bloating score from baseline to week-8 using a 5-point Likert scale . Bloating means subjective abdominal fullness or distension reported by the patient. Bloating score is evaluated on a 5-point Likert scale (From 1 to 5, higher score means worse outcome) | 8 weeks |
| Change in weekly straining score | Change in weekly straining score from baseline to week-8 will be measured using 5-point Likert scale (from 1 to 5, higher score means worse outcome) | 8 weeks |
| Change in weekly abdominal pain or discomfort score | Change in weekly abdominal pain or discomfort score from baseline to week-8 will be measured using 5-point Likert scale (from 1 to 5, higher score means worse outcome) | 8 weeks |
| Change in satisfaction score related to defecation | Satisfaction score related to defecation will be measured using 5-point defecatory satisfaction score (Likert scale, from 1 to 5, lower score means worse outcome) and change will be compared between baseline value and week-8 value. | 8 weeks |
| Patient reported adverse events | Patient-reported adverse events associated with Linaclotide treatment will be documented according to common terminology criteria for adverse events (CTCAE grading). | Through study completion, an average of 10 weeks |
| Sustainability of treatment effects | Sustainability of treatment effects: Sustainability will be defined as maintenance of improved symptom scores during the 2 week drug free follow up period after week-8 at levels that are not statistically significantly worse than end of treatment values and remain no worse than baseline. These symptom scores includes weekly spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) frequency, stool consistency measured by Bristol Stool Form scale (BSFS, from type 1 to 7), abdominal symptom scores including bloating score, straining score, abdominal pain or discomfort scores using 5-point Likert scale (1 to 5, higher score means worse outcome), satisfaction score related to defecation using 5-point Likert scale (1 to 5, Lower score means worse outcome) etc. | 2 week of drug free follow up period (from week-9 to week-10) |
| Potentially rebound of symptoms | Rebound of symptoms: Rebound will be defined as worsening of symptom measures beyond baseline levels during the drug free follow up period. These symptom scores includes weekly spontaneous bowel movement (SBM) and complete spontaneous bowel movement (CSBM) frequency, stool consistency measured by Bristol Stool Form scale (BSFS, from type 1 to 7), abdominal symptom scores including bloating score, straining score, abdominal pain or discomfort scores using 5-point Likert scale (1 to 5, higher score means worse outcome), satisfaction score related to defecation using 5-point Likert scale (1 to 5, Lower score means worse outcome) etc. | 2 week of drug free follow up period (from week-9 to week-10) |
| ID | Term |
|---|---|
| D043183 | Irritable Bowel Syndrome |
| ID | Term |
|---|---|
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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