Gastrointestinal Motility Among Diabetes Patients

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.

Conditions

• Diabetic Autonomic Neuropathy
• Gastrointestinal Motility Disorder
• Diabetes Mellitus
• Change of Transit or Circulation

Interventions

RADIATION

11C Donepezil PET/CT scan

Donepezil binds with high affinity to acetylcholine esterase in the cholinergic synapses. The quantity of density of acetylcholine esterase in the abdominal organs including the intestinal wall are demonstrated by 11C Donepezil PET/CT scan. The PET-signal are measured as Standard-uptake values (SUV) in the internal organs. After 6 hours of fast CT- and PET-scans are performed after injection of iv. contrast and about 500MBq (megabecquerel) \[11C\]donepezil. The CT scan is used for anatomical location of the internal organs. The scan-field includes the heart and the abdominal organs. Total scan time is about 60 minutes.

DEVICE

3D-Transit

3D-Transit: 3D-Transit for minimal invasive and ambulant describing of regional transit times and contractions pattern of the bowel. The motility and the passage time is measured by 3D-Transit The description of location and rotation of the capsule is dynamic and very precise. It permits precise detailed description of the gastrointestinal contraction pattern and regional passage time. 3D-transit consist of three different parts: 1. A wireless electromagnetic capsule to be swallowed by the subject 2. A portable detector plate comprising four sensors worn in a belt around the waist 3. Specific software for visualizing and analyzing data

DRUG

3D-Transit during treatment with Pyridostigmine

3D-Transit and Pyridostigmine: The motility and the passage time is measured by 3D-Transit (as mentioned above) in diabetic patients during administration of Pyridostigmine 60 mg administrated 4 times with 4 hours between each administration. Pyridostigmine is increasing the amount of cholinergic neurotransmitter and is suggested to have a reversible effect on the cholinergic denervation. The mechanism of action of Pyridostigmine in the human body is well-known and the drug is used as a tool to determine if the disturbance in the guts are reversible in diabetic patients.

DEVICE

3D-Transit after Malone appendicostomy

3D-Transit (as earlier described) is performed after Malone appendicostomy. The patients are suppose use the antegrade edema technic during the 3D-transit examination.

Sponsors & Collaborators

• Novo Nordisk A/S

  collaborator INDUSTRY

• Svend Faelding Humanitarian Foundation

  collaborator UNKNOWN

• Copenhagen University Foundation for Medical Students

  collaborator UNKNOWN

• Hoejmosegaard Foundation

  collaborator UNKNOWN

• Holger Rabitz og Hustru Doris Mary foedt Phillipps Mindelegat

  collaborator UNKNOWN

• Lundbeck Foundation

  collaborator OTHER

• Wilhelm Frank og Angelina Franks Mindelegat

  collaborator UNKNOWN

• Torben og Alice Frimodts Fond

  collaborator UNKNOWN

• Fonden til Lægevidenskabens Fremme, A.P. Møller Fonden

  collaborator UNKNOWN

• University of Aarhus

  lead OTHER

Principal Investigators

• Klaus Krogh, Professor · Department of Hepatology and Gastroenterology, Aarhus University Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-10-31

Primary Completion

2019-02-11

Completion

2019-02-11

Countries

• Denmark

Study Locations