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Pathophysiology of Diabetic Gastroparesis (PATODIAG)

Primary Purpose

Gastroparesis Due to Diabetes Mellitus Type I

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
technetium scitigraphy
Sponsored by
Hvidovre University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Gastroparesis Due to Diabetes Mellitus Type I focused on measuring gastroparesis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Type 1 diabetes age 18-85 Case group: Gastroparesis verified by technetium scintigraphy and a GCSI score ≥ 1.9 Control group: Gastroparesis not confirmed by technetium scintigraphy and score GCSI score < 1.9 Exclusion Criteria: Ongoing cancer treatment or other concurrent illness that will make the patient unable to attend the study on the discretion of the investigator. Recent gastrointestinal surgery Active duodenal/gastric ulcer disease, Diseases in the ventricle or previously complicated upper abdominal surgery Pregnancy or breast feeding Persons who, in the judgement of the investigator, may be unable to follow the protocol. Parkinson disease metoclopramide 48 hours prior to scintigraphy domperidone 48 hours prior to scintigraphy macrolide antibiotics 48 hours prior to scintigraphy anti-cholinergic agents Tricycliv antidepressants Glucagon-like peptide-1 analogues Lithium Diphenhydramine dopamine agonists progesterone, L-dopa calcitonine ocreotide Interferon alfa sucralsulfate botulinum toxin injections (eg, Botox®) by pyloric injection.

Sites / Locations

  • Hvidovre University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

cases with gastroparesis

Controls without gastroparesis

Arm Description

patients with a gastroparesis symptom score index (GCSI) of > 1.9 will be considered as cases with gastroparesis and will be subjected to technetium-scintigraphy and gastroscopy with tissuesamples from antrum and fundus and bloodsamples of glucosemetabolism

patients with a gastroparesis symptom score index (GCSI) of < 1.9 will be considered as controls without gastroparesis and will be subjected to technetium-scintigraphy and gastroscopy with tissuesamples from antrum and fundus and bloodsamples of glucosemetabolism

Outcomes

Primary Outcome Measures

mucosal nerve length density (MNLD)
differences in mucosal nerve length density (MNLD) of the gastric fundus and antrum in diabetes patients with and without gastroparesis. MNLD will be assessed by confocal microscopy of mucosal biopsies obtained by oesophago-gastro-duodenoscopy.

Secondary Outcome Measures

Nerve fibre morphology
Nerve fibre morphology assessed by confocal microscopy of mucosal biopsies obtained by esophago-gastro-duodenoscopy
Differences in histology
Hematoxylin and eosin (HE) staining and c-KIT staining of immune cells, interstitial cells, glia cells, ganglion cells and smooth muscle cells and visualization under a microscope
Transcriptional changes
Altered transcriptional changes in mRNA by NanoString.
Differences in cell populations
Differences in cell populations by fluorescence-activated cell sorting (FACS).
Differences in pyloric distensibility
Pyloric distensibility measurements by Endo-Flip.
Differences in glucose metabolism
plasma glucose in mmol/L, HbA1c in mmol/mol, proinsulin C-peptide in pmol/L
Differences in gastric emptying time
Gastric emptying time assessed by technetium scintigraphy.
Differences in neuropathy measures
sensory tests that record sensation of touch, vibration, cooling and heat.
Immunohistochemical differences
Immunohistochemical staining that uses antibodies to visualize the localization of particular proteins within single cells.

Full Information

First Posted
December 12, 2022
Last Updated
April 12, 2023
Sponsor
Hvidovre University Hospital
Collaborators
Zealand University Hospital, Steno Diabetes Center Copenhagen
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1. Study Identification

Unique Protocol Identification Number
NCT05717205
Brief Title
Pathophysiology of Diabetic Gastroparesis
Acronym
PATODIAG
Official Title
Pathophysiology of Diabetic Gastroparesis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hvidovre University Hospital
Collaborators
Zealand University Hospital, Steno Diabetes Center Copenhagen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this study is to explore the pathophysiology of diabetic gastroparesis by conducting an exploratory cohort study. Participants will be type 1 diabetes patients with and without gastroparesis. Investigators will investigate Differences in nervefiber density and morphology Cellular and transcriptional changes and indices of glucosemetabolism between groups
Detailed Description
Aims To perform an exploratory cohort study including 26 type 1 diabetes (DM1) patients aged 18-85 years with gastroparesis and 26 comparable DM1 diabetes patients without gastroparesis, investigating nerve fibre density and length in the mucosal and submucosal layer of the stomach (fundus, and antrum). A variety of molecular, biochemical and cellular experimental procedures will be performed on bloodsamples and tissue biopsies collected during gastroscopy exploring the pathophysiology of gastroparesis. In addition, we will compare differences in, measures of glucose metabolism in the two patient groups through bloodsamples. Hypotheses Nerve fibre morphology in the stomach is different in type 1 diabetes patients with diabetic gastroparesis compared to diabetes patient without gastroparesis and associated with differences in glucose metabolism and the severity of autonomic and peripheral neuropathy. Patients with gastroparesis show loss of interstitial cells of Cajal (ICC) in the gastric body, antrum and fundus and have marked morphological changes indicative of injuries. Macrophages are thought to play a central role in diabetic gastroparesis, in which a loss of anti-inflammatory heme-oxygenase-1 (HO-1) positive macrophages leads to decreased protection against oxidative stress, resulting in damage to ICCs. In gastroparesis there is increased presence of fibrosis in the stroma and alteration in inflammatory cells. Patients with gastroparesis may have decreased levels of neurotransmitters such as NO and substance P. Gastroparesis may cause pathological alterations of enteric glial and ganglion cells and the cytoplasm of smooth muscle cells. Patients with gastroparesis have lower pyloric distensibility. Examining transcriptional changes in between groups will reveal new genes associated with disease development. Newly developed in vitro models make it possible to explore and correlate molecular biochemical and cellular factors to disease development and progression. Study Design All participants will be type 1 diabetes patients attending treatment at Steno Diabetes Center Copenhagen (SDCC) or type 1 diabetes patients referred from other treatment facilities. Patients will fill out the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire and be asked if they have been diagnosed with gastroparesis. Patients with known gastroparesis or with a GCSI score ≥ 1.9 without known gastroparesis will be subject to a technetium scintigraphy. Patients without established gastroparesis and a GCSI score < 1.9 will also undergo technetium scintigraphy. A gastric content above 10%, 4 hours after meal ingestion will be considered the diagnostic threshold for gastroparesis Patients with gastroparesis will be considered as cases and patients without gastroparesis as control. All patients will have a gastroscopy to rule out other causes to gastro-intestinal symptoms. During gastroscopy, 8 biopsies will be obtained and endo-flip will be used to measure distesibility in pylorus. Tissue specimens and blood samples will be collected and used in various research-based analyses to understand the pathophysiology.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastroparesis Due to Diabetes Mellitus Type I
Keywords
gastroparesis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cases with gastroparesis
Arm Type
Active Comparator
Arm Description
patients with a gastroparesis symptom score index (GCSI) of > 1.9 will be considered as cases with gastroparesis and will be subjected to technetium-scintigraphy and gastroscopy with tissuesamples from antrum and fundus and bloodsamples of glucosemetabolism
Arm Title
Controls without gastroparesis
Arm Type
Active Comparator
Arm Description
patients with a gastroparesis symptom score index (GCSI) of < 1.9 will be considered as controls without gastroparesis and will be subjected to technetium-scintigraphy and gastroscopy with tissuesamples from antrum and fundus and bloodsamples of glucosemetabolism
Intervention Type
Diagnostic Test
Intervention Name(s)
technetium scitigraphy
Other Intervention Name(s)
gastroscopy with tissuesamples
Intervention Description
patients will have a technetium scintraphy confirming or ruling out gastroparesis. Then the patients will have a gastroscopy with tissue samples from antrum and fundus. During gastroscopy an endo-flip ballon will meassure the distensibility in pylorus.
Primary Outcome Measure Information:
Title
mucosal nerve length density (MNLD)
Description
differences in mucosal nerve length density (MNLD) of the gastric fundus and antrum in diabetes patients with and without gastroparesis. MNLD will be assessed by confocal microscopy of mucosal biopsies obtained by oesophago-gastro-duodenoscopy.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Nerve fibre morphology
Description
Nerve fibre morphology assessed by confocal microscopy of mucosal biopsies obtained by esophago-gastro-duodenoscopy
Time Frame
24 months
Title
Differences in histology
Description
Hematoxylin and eosin (HE) staining and c-KIT staining of immune cells, interstitial cells, glia cells, ganglion cells and smooth muscle cells and visualization under a microscope
Time Frame
24 months
Title
Transcriptional changes
Description
Altered transcriptional changes in mRNA by NanoString.
Time Frame
24 months
Title
Differences in cell populations
Description
Differences in cell populations by fluorescence-activated cell sorting (FACS).
Time Frame
24 months
Title
Differences in pyloric distensibility
Description
Pyloric distensibility measurements by Endo-Flip.
Time Frame
24 months
Title
Differences in glucose metabolism
Description
plasma glucose in mmol/L, HbA1c in mmol/mol, proinsulin C-peptide in pmol/L
Time Frame
24 months
Title
Differences in gastric emptying time
Description
Gastric emptying time assessed by technetium scintigraphy.
Time Frame
24 months
Title
Differences in neuropathy measures
Description
sensory tests that record sensation of touch, vibration, cooling and heat.
Time Frame
24 months
Title
Immunohistochemical differences
Description
Immunohistochemical staining that uses antibodies to visualize the localization of particular proteins within single cells.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 1 diabetes age 18-85 Case group: Gastroparesis verified by technetium scintigraphy and a GCSI score ≥ 1.9 Control group: Gastroparesis not confirmed by technetium scintigraphy and score GCSI score < 1.9 Exclusion Criteria: Ongoing cancer treatment or other concurrent illness that will make the patient unable to attend the study on the discretion of the investigator. Recent gastrointestinal surgery Active duodenal/gastric ulcer disease, Diseases in the ventricle or previously complicated upper abdominal surgery Pregnancy or breast feeding Persons who, in the judgement of the investigator, may be unable to follow the protocol. Parkinson disease metoclopramide 48 hours prior to scintigraphy domperidone 48 hours prior to scintigraphy macrolide antibiotics 48 hours prior to scintigraphy anti-cholinergic agents Tricycliv antidepressants Glucagon-like peptide-1 analogues Lithium Diphenhydramine dopamine agonists progesterone, L-dopa calcitonine ocreotide Interferon alfa sucralsulfate botulinum toxin injections (eg, Botox®) by pyloric injection.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Melina S Hansen, MD
Phone
+4528304757
Email
melina.svraka.hansen.01@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
John G Karstensen, MD, associate professor
Phone
+4540944465
Email
john.gasdal.karstensen@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melina S Hansen, MD
Organizational Affiliation
Copenhagen University Hospital, Hvidovre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hvidovre University Hospital
City
Hvidovre
State/Province
Region Hovedstaden
ZIP/Postal Code
2650
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melina S Hansen, MD
Phone
+4528304757
Email
melina.svraka.hansen.01@regionh.dk
First Name & Middle Initial & Last Name & Degree
John G Karstensen, MD
Phone
+4540944465
Email
john.gasdal.karstensen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No

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Pathophysiology of Diabetic Gastroparesis

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