Effect of ROSE-010 on Gastrointestinal Motor Functions in Female Patients With Constipation Predominant Irritable Bowel Syndrome (C-IBS)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Colonic Transit, Colonic Geometric Center at 24 Hours
研究概览
简要总结
This trial will study the effects of an investigational (not FDA approved) medication, ROSE-010, on the movement of food through the stomach, small intestine and colon in females with constipation predominant irritable bowel syndrome (C-IBS).
The study hypothesis is that ROSE-010 will delay gastric emptying of solids and enhances gastric accommodation without retarding colonic transit in female patients with C-IBS.
详细描述
Methodology
Female patients with C-IBS will be screened for eligibility and informed about the study at the initial screening visit Visit 1. Within two weeks of Visit 1, eligible patients will be randomized to study medication, either 30 mcg, 100 mcg or 300 mcg ROSE-010 or placebo administered via abdominal subcutaneous (s.c.) injection for a total of four days, three consecutive days during transit scintigraphy and once prior to SPECT imaging. The allocation to treatment group will be concealed.
Study medication will be administered at Visits 2, 3, and 4, the days of scintigraphic assessment of gastric, small bowel and colonic transit of solids performed over a 48 hour period.
Within two to seven days of Visit 4, patients will be instructed to return for administration of a final injection of study medication followed by SPECT gastric accommodation measurements (Visit 5). Within seven to ten days of Visit 5, patients will return for Visit 6, final safety monitoring and an exit interview with study staff.
Investigational product, dosage and mode of administration
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Female patients who are pregnant or breast-feeding.
- •Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders other than C-IBS.
- •Unable to withdraw medications 48 hours prior to the study: any medication that alters GI transit including but not limited to laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors (SNRIs); analgesic drugs including opiates, nonsteroidal anti-inflammatory drugs (NSAIDs), and COX 2 inhibitors (Note: Tylenol is permitted), GABAergic agents and benzodiazepines. Note: All other concomitant medications will be reviewed on a case by case basis by the study physicians.
- •Clinical evidence (including but not limited to a clinically significant abnormal physical exam, ECG or laboratory result in the past medical record) or current clinically significant abnormal physical exam or laboratory test result that could indicate significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other diseases that interfere with the objectives of the study. If a laboratory test result is abnormal and clinically significant, it may be repeated once at the discretion of the PI. If the laboratory test result remains abnormal and clinically significant, the patient will be referred to a primary care physician for further evaluation.
- •Patients who are considered by the Investigator to be alcoholics not in remission or known substance abusers.
- •Patients who have participated in another clinical study within the past 30 days.
研究组 & 干预措施
ROSE-010 30 mcg
A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 30 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.
干预措施: ROSE-010 (Drug)
ROSE-010 100 mcg
A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 100 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.
干预措施: ROSE-010 (Drug)
ROSE-010 300 mcg
A glucagon-like peptide-1 (GLP-1) analogue. A glucagon-like peptide-1 (GLP-1) analogue. Subjects received a ROSE-010 300 mcg subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.
干预措施: ROSE-010 (Drug)
Placebo
Subjects received a matching placebo subcutaneous injection daily for 3 consecutive days and on 1 day 2-10 days later.
干预措施: Placebo (Drug)
结局指标
主要结局
Colonic Transit, Colonic Geometric Center at 24 Hours
时间窗: 24 hours (Visit 3 = Day 1)
The scintigraphic method is used to measure colonic transit. An isotope is adsorbed on activated charcoal particles and delivered to the colon in a delayed release capsule. Anterior and posterior gamma images are taken hourly. The geometric center (GC) is the weighted average of counts in the different colonic regions. The scale ranges from 1 to 5; a high GC implies faster colonic transit, a GC of 1 implies all isotope is in the ascending colon, and a GC of 5 implies all isotope is in the stool.
Change Between Postprandial and Fasting Whole Gastric Volume by Technetium-99m (99mTc)-SPECT Imaging (Gastric Accommodation)
时间窗: approximately 1 hour after 99mTC injection, approximately 30 min after liquid meal (Visit 5 = approximately 2-10 days after Visit 4)
A noninvasive SPECT method was used to measure gastric volume during fasting and 32 min after a liquid nutritional supplement meal. Subjects reported to the clinic after an overnight fast. 99mTC was giving by an intravenous injection in the forearm. The first fasting scan was obtained, and the study medication was given s.c. After 10 min, a 2nd fasting post medication scan was obtained, and the meal consumed; then two serial postprandial scans were obtained. Each scan required 9-12 min. Tomographic images of the gastric wall were obtained throughout the long axis of the stomach using a dual-head gamma camera that rotates around the body. This allows assessment of the radiolabeled circumference of the gastric wall, rather than the intragastric content. For this outcome measure, the scans for the "fasting volume" and 2 "postprandial volumes" were used. The 2 postprandial (PP) volumes were averaged. Change was calculated as (PP - Fasting = gastric accommodation).
Half Time (t1/2) of Gastric Emptying of Solids Measured by Scintigraphy (Gastric Transit)
时间窗: approximately 2 hours after radiolabeled meal is ingested (Visit 2 = Day 0)
Half time (t1/2) of gastric emptying (GE) of solids is the time for half of the ingested solids or liquids to leave the stomach. The scintigraphy for GE t1/2 was done on Visit 2 (Day 0 of the study), the first day of scintigraphy.
次要结局
- Gastric Residual at 2 and 4 Hours Measured by Scintigraphy(2 hours, 4 hours (Visit 2 = Day 0))
- Colonic Geometric Center at 4 h Measured by Scintigraphy(4 hours (Visit 2 = Day 0))
- Colonic Filling at 6 h Measured by Scintigraphy(6 hours (Visit 2 = Day 0))
- Ascending Colon Emptying Half-time (AC t1/2) Measured by Scintigraphy(48 hours (Visit 4 = Day 2))
- Colonic Transit, Colonic Geometric Center at 48 h Measured by Scintigraphy, as Compared to Placebo.(48 hours (Visit 4 = Day 2))
- Stool Frequency(screening visit (Visit 1), 34 days (Visit 6))
- Stool Consistency Post Treatment(34 days (Visit 6))