Gastrointestinal Motility Among Diabetes Patients

• Status: Terminated
• Trial end date: 2019-02-11
• Target enrollment: 0
• Participant gender: All

Summary

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.

1. With [11C]donepezil PET/CT, we aim to describe the degree of cholinergic denervation of the intestine in DM patients with GI severe symptoms.

2. 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.

3. 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.

4. 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.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Aarhus
• Collaborators: Copenhagen University Foundation for Medical Students; Fonden til Lægevidenskabens Fremme, A.P. Møller Fonden; Hoejmosegaard Foundation; Holger Rabitz og Hustru Doris Mary foedt Phillipps Mindelegat; Lundbeck Foundation; Novo Nordisk A/S; Svend Faelding Humanitarian Foundation; Torben og Alice Frimodts Fond; Wilhelm Frank og Angelina Franks Mindelegat
• Treatments: Acetylcholine; Donepezil; Pyridostigmine Bromide

Criteria

Inclusion Criteria: (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

Exclusion Criteria:

• 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