Efficacy and Safety of Lubiprostone in the Treatment of Slow Transit Constipation

Efficacy and Safety of Lubiprostone in the Treatment of Slow Transit Constipation: A Multicenter, Randomized Controlled Trial

Lubiprostone has established efficacy and a favorable safety profile in chronic constipation and irritable bowel syndrome with constipation (IBS-C). However, clinical data specifically supporting its use in slow-transit constipation (STC), a distinct subtype of chronic constipation, remains limited.

Slow-transit constipation (STC) is a common subtype of chronic constipation, accounting for up to 30% of cases. Its clinical hallmarks include a diminished or absent urge to defecate and a significantly reduced stool frequency (spontaneous bowel movements <3 per week). The condition often follows a prolonged and progressively worsening course, characterized by straining, passage of hard stools, and associated symptoms such as abdominal pain and bloating. In severe cases, fecal impaction and consequent colonic obstruction may occur, substantially impairing the patient's quality of life.

Non-surgical management, including lifestyle modifications, pharmacological therapy, gut microbiome modulation, and sacral nerve stimulation, remains the first-line approach for most STC patients. Among these, pharmacotherapy is central. Conventional agents include bulk-forming, osmotic, and stimulant laxatives, as well as prokinetics. However, these options are often limited by adverse effects-such as abdominal pain, bloating, rash, drug dependence, malabsorption, and electrolyte imbalances-and the development of tolerance with long-term use. This frequently leaves patients with inadequate relief, creating an urgent need for more effective and safer therapeutics.

Lubiprostone, a chloride channel activator that functions as a secretagogue, enhances intestinal fluid secretion and motility. Its efficacy and safety in chronic idiopathic constipation and irritable bowel syndrome with constipation are well-documented, leading to approvals by the U.S. FDA for these indications. Nevertheless, specific data on its use for STC, a distinct pathophysiological entity, is lacking. This study is therefore designed to evaluate the clinical efficacy and safety of lubiprostone in an STC population, with the aim of generating new evidence to inform precise treatment strategies for this condition.

Inclusion Criteria:

1. Patients voluntarily participated in the study and provided signed informed consent;
2. Met the Rome IV diagnostic criteria for functional constipation;
3. Had fewer than 3 spontaneous bowel movements (SBMs) per week;
4. More than 20% the radio-paque markers localized in the colon after 72 hours based on colonic transit studies;
5. Were able to complete the bowel movement diary and study questionnaires as required by the study protocol;
6. Agreed to use effective contraception from the time of signing the informed consent form until 3 months after the last dose of the study drug;
7. Aged 18 years or older, both males and females.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with severe outlet obstruction constipation (e.g. Oxford Grade IV or above for rectal prolapse, rectocele > 3.1 cm, puborectalis syndrome).
3. Patients with hyperthyroidism or hypothyroidism.
4. Patients with opioid-induced constipation.
5. Patients with megacolon or megarectum.
6. Patients with apparent mechanical intestinal obstruction.
7. Patients with inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis).
8. Patients with malignant tumors of the digestive system.
9. Patients with a history of colorectal surgery.
10. Patients with a previous history of taking lubiprostone.
11. Patients with severe symptoms of depression or anxiety.
12. Patients with known or suspected hypersensitivity to lubiprostone/polyethylene glycol 4000 or any excipients.
13. Patients requiring medications for Parkinson's disease, antipsychotics, antimanic agents, or psychostimulants.
14. Patients with severe cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurological, or psychiatric diseases.
15. Other patients deemed by the investigator as unsuitable for participation in this trial.