Pyridostigmine in Diabetics With Constipation: Randomized, Placebo-controlled, Double-blind Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy
研究概览
简要总结
Doctors at Mayo Clinic are doing this study to learn if pyridostigmine, a drug, affects the speed at which food travels through the stomach, intestines and colon, and if pyridostigmine improves constipation symptoms in patients with diabetes. Pyridostigmine has been approved by the Food and Drug Administration (FDA) for routine clinical use, however, its use as proposed in this study is considered investigational.
详细描述
Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. The study evaluated the effects of a cholinesterase inhibitor (pyridostigmine vs. placebo) on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation.
After a 9-day baseline period, patients with diabetes mellitus and chronic constipation without defecatory disorder will be randomized to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose of 120 mg three times a day; this dose will be maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function will be evaluated at baseline and the final 3 and 7 days of treatment, respectively.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects with diabetes mellitus (Type I or type II), diagnosed by a physician.
- •On medical treatment for diabetes (oral medication or injected insulin) for at least one year
- •Symptomatic constipation at least 25% of the time in the past year (Rome II criteria for functional constipation)
- •18-70 years of age
- •Colonoscopy negative for obstructive lesions, cancer, or inflammatory bowel disease (IBS) within the last 8 years if 50 years of age or older
- •Able to provide written informed consent before participating in trial
- •Able to communicate adequately with the Investigator and to comply with the requirements for the entire study
排除标准
- •History of pelvic floor dysfunction (other functional GI disorders, eg IBS, non-ulcer dyspepsia are acceptable); Specifically, patients will be excluded if they have at least 2 of the following 3 criteria:
- •History of digital evacuation of the rectum or pressure on the posterior aspect of the vagina or perineum to facilitate defecation
- •Examination findings suggestive of puborectalis spasm or anismus, on assessment by an experienced gastroenterologist with expertise in this field; i.e. high anal sphincter tone at rest, failure of perineal descent by >1cm on straining, and tenderness or paradoxical contraction of the puborectalis on digital examination
- •Requirement of > 200g to expel a rectal balloon during voluntary straining
- •Abdominal surgery other than appendectomy, cholecystectomy, hysterectomy, tubal ligation, or inguinal hernia repair
- •Suspected or known gastrointestinal or genitourinary obstruction
- •Uncontrolled hypertension (defined as > 150/90 at rest)
- •Known cardiac arrhythmia or ECG abnormalities, i.e. cardiac conduction disturbances (2nd or 3rd degree atrioventricular (AV) block, prolonged corrected QT interval (QTc)(> 460 msec) or bradycardia (< 45 beats/minute))
- •Renal insufficiency with serum creatinine greater than 2 mg/dl based on a reading from the previous 6 months
- •Asthma or chronic obstructive pulmonary disease requiring systemic steroids in the previous 3 years (inhaled steroids acceptable)
- •Current use of narcotics, gut prokinetic drugs (eg metoclopramide, domperidone, tegaserod, senekot), anticholinergic medication (eg. Hyoscyamine, belladonna), antidiarrheals (Imodium, Lomotil), or laxatives other than fiber supplements, docusate, or glycerin suppositories. Patients on any of these restricted medications must cease use at least 48 hours before starting and for the duration of both study phases. No rescue laxatives will be permitted within 7 days of transit testing
- •Patients who have taken any investigational medications within the past 30 days
- •Known intolerance or allergy to eggs
- •Pregnant or breast-feeding females
研究组 & 干预措施
Pyridostigmine
Oral pyridostigmine, starting with 60 mg capsules three times per day (TID), increasing by 60 mg every third day (i.e., over 10 days) up to the maximum tolerated dose or 120 mg TID (a total of 360 mg per day). This dose was maintained for 7 days.
干预措施: Pyridostigmine (Drug)
Placebo
Placebo (sham) capsules, matching the appearance of the active drug comparator and taken TID.
干预措施: Placebo (Drug)
结局指标
主要结局
Colonic Geometric Center at 24 Hours (GC24) Measured by Scintigraphy
时间窗: Baseline period (days 7-9 ), Treatment period (days 14-17)
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 of the abdomen are taken hourly for the first 6 hours after the radio-labeled meal, then at 8, 24 and 48 hours. 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. GC24 is the measurement taken at 24 hours after the radio-labeled meal.
Ascending Colon Emptying Half-time (AC t1/2) Measured in Hours
时间窗: Baseline period (days 7-9 ), Treatment period (days 14-17)
Calculated by linear interpolation of values on the AC emptying curve.
次要结局
- Gastric Emptying Half-time (GE t1/2)(Baseline period (9 days), Treatment period (7 days))
- Colonic Filling at 6 Hours(Baseline period (9 days), Treatment period (7 days))
- Colonic Geometric Center at 48 Hours (GC48) as Measured by Scintigraphy(Baseline period (days 7-9 ), Treatment period (days 14-17))
- Stool Frequency Per Day(Daily during baseline period (9 days), Treatment period (7 days))
- Stool Form/Consistency(Daily during baseline period (9 days), Treatment period (7 days))
- Stool Ease of Passage(Daily during baseline period (9 days), Treatment period (7 days))
- Sense of Completely Emptying Bowels(Daily during baseline period (9 days), Treatment period (7 days))
- Stool Frequency Per Week(Daily during baseline period (9 days), Treatment period (7 days))
- Heart Rate Before and After Treatment(Baseline period (9 days), Treatment period (7 days))
- QTc Interval Before and After Treatment(Baseline period (9 days), Treatment period (7 days))
研究者
Adil Bharucha
MD, Professor of Medicine
Mayo Clinic