Efficacy of Linaclotide in Patients With Overlapping Functional Gastrointestinal Disorders

After being informed about the content and risks of the research, all eligible patients giving written informed consent will be randomly allocated in a 2:1 ratio to linaclotide (290μg, once daily) or lactulose (20mL, once daily). Treatment will last consecutively for 4 weeks, and patients' symptoms will be assessed before and after four-week treatment.

• Linaclotide (Drug), also known as Linzess: 290μg once daily, 4 weeks
• Lactulose (Drug), also known as Duphalac: 20mL once daily, 4 weeks
• Omeprazol (Drug): 20mg twice daily for the first 10 days
• Itopride (Drug): 50mg three times daily for the first 10 days

Primary outcomes

• Treatment satisfaction assessed by the VAS [Week 4]: Treatment satisfaction will be assessed by the Visual Analogue Scale: score 0=not at all, 1=partial relief of general GI symptoms, 2=complete relief of general GI symptoms.

Secondary outcomes

• Changes in stool frequency [Baseline and Week 4]: Stool frequency will be assessed using bowel movement (BM), spontaneous bowel movement (SBM), complete spontaneous bowel movement (CSBM) during the past 7 days. Change = (Week 4 Score - Baseline Score).
• Changes in stool consistency [Baseline and Week 4]: Stool consistency will be assessed using Bristol Stool Form Scale (BSFS), which contains 7 types of stool consistency. Change = (Week 4 Score - Baseline Score).
• Changes in defecation straining score [Baseline and Week 4]: Defecation straining score will be assessed using six-point scale (score 0 = effortless, 5 = extremely laborious). Change = (Week 4 Score - Baseline Score).
• Changes in defecation time [Baseline and Week 4]: Defecation time will be assessed using approximate duration: less than 15 minutes, 15-30 minutes, more than 30 minutes.
• Changes in sensation of complete evacuation [Baseline and Week 4]: Sensation of complete evacuation will be assessed using five-point scale (score 0 = not at all, 4 = complete totally). Change = (Week 4 Score - Baseline Score).
• Changes in lower abdominal discomfort [Baseline and Week 4]: Lower abdominal discomfort will be assessed using six-point scale (score 0 = not at all, 5 = extremely severe). Change = (Week 4 Score - Baseline Score).
• Changes in lower abdominal pain [Baseline and Week 4]: Lower abdominal pain will be assessed using six-point scale (score 0 = not at all, 5 = extremely severe). Change = (Week 4 Score - Baseline Score).
• Changes in FD symptoms [Baseline and Week 4]: FD symptoms will be assessed using Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM). Change = (Week 4 Score - Baseline Score).
• Changes in the anxiety status [Baseline and Week 4]: The anxiety status will be assessed using the Generalized Anxiety Disorder scale (GAD-7). Change = (Week 4 Score - Baseline Score).
• Changes in the depression status [Baseline and Week 4]: The depression status will be assessed using the Patient Health Questionnaire (PHD-9). Change = (Week 4 Score - Baseline Score).

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

Inclusion Criteria:

1. Outpatients
2. Diagnosis of FD (including postprandial distress syndrome \[PDS\] with or without epigastric pain syndrome \[EPS\]) (Rome Ⅲ criteria)
3. Diagnosis of IBS-C (Rome Ⅲ criteria)

Exclusion Criteria:

1. Helicobacter Pylori infection
2. GI symptoms caused by taking non-steroidal anti-inflammatory drugs or other agents
3. Pregnancy

• Results publication: Cheng L, Wang Q, Wu B, Yan X, Xu P, Qiu H, Chen S. Efficacy of Linaclotide in Functional Dyspepsia and Constipation-Predominant Irritable Bowel Syndrome Overlap: A Randomized Trial. J Gastroenterol Hepatol. 2025 May;40(5):1119-1127. doi: 10.1111/jgh.16925. Epub 2025 Mar 13. PMID 40079184

• Shengliang Chen, Principal investigator, RenJi Hospital