"Efficacy and Safety of Linaclotide in Chronic Constipation"

Phase 4Not Yet RecruitingNCT07431957

Md Mehedi Shahriar90 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patients (18-70 years) * patients diagnosed with CIC or IBS-C based on Rome IV criteria * No abnormal finding on colonoscopy conducted within past 1 year * Patients who can read and are willing to complete daily bowel diary and follow study procedures Exclusion Criteria: * Clinical features suggestive of organic disease ( Anaemia, unexplained weight loss, per rectal bleeding, family history of malignancy) * Secondary constipation due to structural, metabolic, or neurological causes (IBD, Colorectal cancer, hypothyroidism, hypercalcemia, DM, Parkinson's disease) * History of or new onset intestinal obstruction * Prior history of stomach, small intestine and colorectal surgery ( except appendectomy or hemorroidectomy) * Patients currently suffering from medication induced costipation ( opioids, anti choline raids, calcium channel blockers, oral iron and calcium supplements, anti-Parkinsonian drug, antipsychotic, anti-emetics or psychostimulant drugs) * Use of medication affecting bowel motility ( Lubiprostone, Elobixibat, PEG or prosecretory agents) within 2 week before enrollment * Serious cardiovascular, respiratory, renal, GI, hepatic, hematological, neurological or psychiatric illness * Pregnancy or lactation

Outcomes

Primary Outcomes

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.

Time frame: 8 weeks

Secondary Outcomes

Mean change in weekly SBM frequency

Mean change in weekly Spontaneous Bowel Movement (SBM) after 8 weeks from baseline.

Time frame: 8 weeks

Mean change in CSBM frequency

Mean change in weekly Complete Spontaneous Bowel Movement (CSBM) after 8 weeks from baseline

Time frame: 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).

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 2 week of drug free follow up period (from week-9 to week-10)

"Efficacy and Safety of Linaclotide in Chronic Constipation"

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts