Efficacy and Safety of Lubiprostone in the Treatment of Slow Transit Constipation: A Multicenter, Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 346
- 试验地点
- 23
- 主要终点
- The change in spontaneous bowel movements (SBMs) frequency from baseline during the first week
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients voluntarily participated in the study and provided signed informed consent;
- •Met the Rome IV diagnostic criteria for functional constipation;
- •Had fewer than 3 spontaneous bowel movements (SBMs) per week;
- •More than 20% the radio-paque markers localized in the colon after 72 hours based on colonic transit studies;
- •Were able to complete the bowel movement diary and study questionnaires as required by the study protocol;
- •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;
- •Aged 18 years or older, both males and females.
排除标准
- •Pregnant or lactating women.
- •Patients with severe outlet obstruction constipation (e.g. Oxford Grade IV or above for rectal prolapse, rectocele > 3.1 cm, puborectalis syndrome).
- •Patients with hyperthyroidism or hypothyroidism.
- •Patients with opioid-induced constipation.
- •Patients with megacolon or megarectum.
- •Patients with apparent mechanical intestinal obstruction.
- •Patients with inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis).
- •Patients with malignant tumors of the digestive system.
- •Patients with a history of colorectal surgery.
- •Patients with a previous history of taking lubiprostone.
- •Patients with severe symptoms of depression or anxiety.
- •Patients with known or suspected hypersensitivity to lubiprostone/polyethylene glycol 4000 or any excipients.
- •Patients requiring medications for Parkinson's disease, antipsychotics, antimanic agents, or psychostimulants.
- •Patients with severe cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematologic, neurological, or psychiatric diseases.
- •Other patients deemed by the investigator as unsuitable for participation in this trial.
研究组 & 干预措施
Polyethylene Glycol
Polyethylene glycol (PEG ) is an established osmotic laxative, widely available worldwide for the treatment of functional constipation in adults and children.
干预措施: Polyethylene glycol (PEG ) (Drug)
Lubiprostone
Lubiprostone is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of human gastrointestinal epithelial cells, thereby increasing chloride-rich fluid secretion. Although the mechanism is unclear, this may then decrease intestinal transit time, allowing the passage of stool and alleviating symptoms of constipation.
干预措施: Lubiprostone (Drug)
结局指标
主要结局
The change in spontaneous bowel movements (SBMs) frequency from baseline during the first week
时间窗: From 2 weeks prior to the first dose through 4 weeks after treatment initiation
The change from baseline in the weekly average number of SBMs reported during the first week after treatment initiation
次要结局
- The percentage of patients with SBMs within 24 hours after the first intake of the study drug(Day 1 after treatment initiation)
- Time to first SBM occurrence after treatment initiation(Up to 4 weeks after treatment initiation)
- The percentage of patients reporting 3 or more SBMs/wk(From 2 weeks prior to the first dose through 4 weeks after treatment initiation)
- The percentage of patients achieving an increase of ≥1 SBMs/week from baseline(From 2 weeks prior to the first dose through 4 weeks after treatment initiation)
- The change from baseline in the weekly average number of SBMs at weeks 2, 3, and 4(From 2 weeks prior to the first dose through 4 weeks after treatment initiation)
- The change from baseline in the Bristol Stool Form Scale (BSFS) values for SBMs at weeks 1 and 4(The 1 and 4-week treatment period has been completed)
- The change from baseline in the ratings of straining associated with SBMs at weeks 1 and 4(The 1 and 4-week treatment period has been completed)
- The change from baseline in the Wexner constipation score at weeks 1 and 4(The 1 and 4-week treatment period has been completed)
- The change from baseline in the Patient Assessment of Constipation Quality of Life (PAC-QOL) score at weeks 1 and 4(The 1 and 4-week treatment period has been completed)
- The patients' satisfaction scores at weeks 1 and 4(The 1 and 4-week treatment period has been completed)
- The rate of adverse reactions, including nausea, diarrhea, and abdominal pain.(Up to 4 weeks after treatment initiation)
研究者
Weidong Tong
Director
Third Military Medical University