Gastrointestinal Motility Among Diabetes Patients
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Difference in Donepezil standard-uptake values (SUV) for the small intestine between diabetic patients and healthy subjects.
研究概览
简要总结
Gastrointestinal (GI) symptoms including vomiting, nausea, abdominal pain, constipation or chronic diarrhea affect a large number of patients with diabetes mellitus (DM). Furthermore, abnormal GI transit times restrict correct dosing of medication. Two new methods, in combination only available at Aarhus University Hospital (AUH), allow examination of human whole-gut function with a high degree of detail:
PET-scans (positron emission tomography scans) of cholinergic signaling in the bowel wall The most important nerve fibers stimulating GI peristalsis use acetylcholine as neurotransmitter. The novel PET technique, [11C] Donepezil PET/CT (Donepezil PET/CT scan based on a carbon isotope), developed at AUH, allows in vivo quantification of cholinergic cells within the bowel wall.
3D-Transit With 3D-Transit electromagnetic capsules are followed during their passage through the GI tract. The novel method provides highly detailed information about regional and whole-gut passage times and contractility patterns.
Study protocol 20 healthy subjects and 25 diabetic patients with severe GI symptoms will be included.
- With [11C]donepezil PET/CT, we aim to describe the degree of cholinergic denervation of the intestine in DM patients with GI severe symptoms.
- Using 3D-Transit in DM patients before and during intervention with acetyl cholinesterase inhibitor we aim to determine how cholinergic denervation of the intestine contributes to abnormal GI transit patterns.
- Comparing the transit times of DM patients with either vomiting or diarrhea as main symptoms, we aim to provide pilot data on phenotypes of diabetic GI dysfunction.
- We aim to explore various aspects of "pan-enteric" dysfunction in DM, including prolonged gastric emptying secondary to severe constipation and delayed small intestinal transit in patients with symptoms of gastroparesis with or without delayed gastric emptying
Perspectives Detailed information about cholinergic denervation in DM and objective classification of the pathophysiology of diabetic GI dysfunction may allow targeted future treatment of individual patients.
详细描述
Background GI symptoms are extremely common in patients with DM, often with severe consequences for daily activities, ability to work and quality of life. Moreover, GI-dysfunction causes unpredictable absorption of food and oral medication thus making blood-glucose difficult to control and oral medication less effective. Despite of this fact, the pathophysiology of diabetic bowel dysfunction is only scantily described. Rational treatment of GI motility disorders requires detailed knowledge of the underlying mechanisms and the importance of whole-gut evaluation of patients with motility disorders is increasingly recognized.
Contractions of the GI tract are primary stimulated by cholinergic parasympathetic nerves (from the vagus nerve and the sacral nerves) or cholinergic nerves in the enteric nerve system located between the muscle layers in the bowel wall. It is likely that cholinergic denervation is a major factor behind the development of GI dysfunction in DM.
Through collaboration between basic physiologist and clinical researchers we are in the unique international position of having two highly advanced methods for description of GI innervation and motility:
A. [11C]donepezil (Donepezil connected with a carbon isotope) PET tracer to quantify the density of acetylcholine esterase in abdominal organs, including the intestinal wall. The method constitutes the first-ever validated scan-method for in vivo measuring cholinergic denervation of the GI tract.
B. 3D-Transit for minimal invasive and ambulant describing of regional transit times and contractions pattern of the bowel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- 是
入选标准
- •(only patients)
- •Subject is suffering from diabetes
- •Gastrointestinal symptoms including diarrhoea, nausea, vomiting, bloating and abdominal discomfort)
- •Subject > 18 years of age who possess capacity to understand subject information sheet and give informed consent for participation
- •Fasted since midnight until morning 8 o´clock
排除标准
- •Dysregulated metabolic disease
- •Structuring bowel disease or obvious stenotic symptoms or perforation
- •Subject has known swallowing disorders
- •Subject has cancer or other life threatening diseases or conditions
- •Subject is pregnant or breastfeeding
- •Subject has undergone extensive abdominal surgery
- •Subject has a abdominal diameter > 140 cm
- •Drug abuse or alcoholism
- •Bacterial overgrowth
- •Subject has known severe cardiovascular or pulmonary diseases (including artificial pacemaker and/or implantable cardioverter-defibrillator (ICD))
- •Central nerve system (CNS) surgery
- •Patient have infusion pump or other implantable medical device
- •Medication (not possible for pausing for 48 hours) or any other disease affecting motility or/and gastroparesis.
- •Subjects having MRI within the next four weeks
- •Taking corticosteroids during the last month
- •Allergic reaction to Pyridostigmine and/or intravenously administrated contrast
- •Severe upper gastrointestinal pathology seen by endoscopy
- •Blood glucose below 4 mmol/L or higher than 10 mmol/L right before examination
- •Bile acid malabsorption or malabsorption in general
- •Obstruction of the urinary system
- •Severe renal insufficiency (eGFR < 45)
- •Peritonitis
研究组 & 干预措施
Diabetic patient
The study consists of four different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
- 3D-Transit during treatment with pyridostigmine
- 3D-Transit after Malone appendicostomy (only diabetic patients who had a Malone-surgery for severe obstipation ordered during standard clinical practice)
干预措施: 11C Donepezil PET/CT scan (Radiation)
Diabetic patient
The study consists of four different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
- 3D-Transit during treatment with pyridostigmine
- 3D-Transit after Malone appendicostomy (only diabetic patients who had a Malone-surgery for severe obstipation ordered during standard clinical practice)
干预措施: 3D-Transit (Device)
Diabetic patient
The study consists of four different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
- 3D-Transit during treatment with pyridostigmine
- 3D-Transit after Malone appendicostomy (only diabetic patients who had a Malone-surgery for severe obstipation ordered during standard clinical practice)
干预措施: 3D-Transit during treatment with Pyridostigmine (Drug)
Diabetic patient
The study consists of four different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
- 3D-Transit during treatment with pyridostigmine
- 3D-Transit after Malone appendicostomy (only diabetic patients who had a Malone-surgery for severe obstipation ordered during standard clinical practice)
干预措施: 3D-Transit after Malone appendicostomy (Device)
Healthy subjects
The study consists of two different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
干预措施: 11C Donepezil PET/CT scan (Radiation)
Healthy subjects
The study consists of two different parts:
- 11C Donepezil PET/CT scan
- 3D-Transit
干预措施: 3D-Transit (Device)
结局指标
主要结局
Difference in Donepezil standard-uptake values (SUV) for the small intestine between diabetic patients and healthy subjects.
时间窗: Through study completion, an average of 1 year
The PET signal is measured as standard-uptake values (SUV) in the internal organs. This simple value has earlier been validated as equivalent to more advanced PET kinetic parameters, were an arterial-needle is required. From the CT-scan volume-of-interests of the relevant organs are applied (bowel segments, heart, pancreas) and the SUV-values draw from the PET-scans. SUV in the small intestine are compared between healthy subjects and diabetic patients. SUV is a measure of in vivo quantification of cholinergic cells in the small bowel.
Difference in total gastrointestinal transit time between diabetic patients and healthy subjects
时间窗: Through study completion, an average of 1 year
The following parameters are analyzed: Total gastrointestinal transit time (capsule number 1). Data from capsule 1 in healthy subjects and diabetic patients will be used for: Comparison of total GI transit times and transit patterns in healthy individuals and diabetic patients.
次要结局
- Measurement of gastric amplitudes(Through study completion, an average of 1 year)
- Measurement of fast movements in the small intestine(Through study completion, an average of 1 year)
- Measurement of mass movements in colorectum(Through study completion, an average of 1 year)
- Difference in total gastrointestinal transit times in diabetic patients´s 3D-transit with and without Pyridostigmine(Through study completion, an average of 1 year)
- Difference in regional intestinal transit times between diabetic patients and healthy subjects(Through study completion, an average of 1 year)
- Difference in regional transit times in diabetic patients´s 3D-transit with and without Pyridostigmine(Through study completion, an average of 1 year)
- Difference in regional transit times in diabetic patients´s 3D-transit before and after Malone antegrade continence enema(Through study completion, an average of 1 year)