A RANDOMISED, PLACEBO-CONTROLLED, CROSSOVER STUDY TO EVALUATE THE EFFECT OF LINACLOTIDE ON COLONIC MOTILITY ASSESSED WITH INTRALUMINAL COLONIC MANOMETRY IN HEALTHY SUBJECTS
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 10
- 主要终点
- Colonic motor patterns during Linaclotide or Placebo administration in healthy subjects.
研究概览
简要总结
This study aim was to evaluate the effect of Linaclotide, a pharmacological treatment normally used to treat functional constipation or irritable bowel syndrome with predominant constipation, on colonic motility as assessed by high-resolution colonic manometry.
详细描述
Rationale: Several treatments with different modes of action are currently available for chronic constipation, including the osmotic laxative polyethylene glycol (PEG), the stimulant laxative bisacodyl, the prokinetic prucalopride and the secretagogue linaclotide. In a previous study conducted in our lab (study S54750) it has been hypothesized that only bisacodyl and prucalopride activate colonic motility. However the results have demonstrated that PEG, bisacodyl and prucalopride did not differ in their effect on colonic motility index, except for bisacodyl which induced HAPCs in a greater number of healthy subjects as compared to both prucalopride and PEG. To our knowledge, the effect of linaclotide on colonic motility has never been studied in humans.
Objectives: Primary: to evaluate the effects of linaclotide as compared to placebo on motility index and on the number of colonic high amplitude propagated contractions (HAPCs) during a 8-hour intraluminal manometry in healthy subjects. Secondary: to evaluate the association between motility parameters and sensations (abdominal gas, desire to defecate, urgency to defecate and abdominal discomfort) as well as number and consistency of bowel movements.
Investigational product, dose, and mode of administration: Regimen A: 290 μg linaclotide once daily oral administration with 125mL of water. Regimen B: placebo, empty capsule, once daily oral administration with 125mL of water.
Methodology: This is randomized, placebo controlled, 2-period cross-over study investigating the effects of placebo and linaclotide on colon motility with intraluminal manometry. On each of Treatment Period, a manometry catheter will be placed in the colon under conscious sedation and the colonic pressure will be continuously measured through 8 hours after administration of each of the investigational products (Regimen A or B).
Inclusion criteria: healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy male and non-pregnant, non-breastfeeding female participants, aged 18-65 years old at the time of consent
排除标准
- •use of medications within 48 h of dose initiation; structural or metabolic diseases that affect the gastrointestinal system and functional gastrointestinal disorders; previous abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, or hernia repair; known illnesses such as diabetes, cardiovascular or lung disease; use of agents that influence bowel habit, i.e. anticholinergics (not including antihistamines with anticholinergic properties), spasmolytics and prokinetics in the 7 days before the study
研究组 & 干预措施
Linaclotide
290 μg linaclotide once daily oral administration with 125mL of water
干预措施: Linaclotide 290 micrograms (Drug)
Placebo
placebo, empty capsule, once daily oral administration with 125mL of water
干预措施: Placebo (Drug)
结局指标
主要结局
Colonic motor patterns during Linaclotide or Placebo administration in healthy subjects.
时间窗: during a 12-hour intraluminal manometry]
Number of colonic high amplitude propagated contractions (HAPCs)
次要结局
- Association between motility parameters and number and consistency of bowel movements in healthy subjects(during a 12-hour intraluminal manometry])