PET Imaging to Delineate Macrophage Activation in Diabetic Gastroparesis

Study Overview
=================
Brief Summary
-----------------
Macrophage-driven immune dysregulation has been shown to be involved in pathophysiology of diabetic gastroparesis. Currently, there are no non-invasive ways to study macrophage activation in humans. The researchers are trying to determine the utility of 11C-ER176 based PET-CT scanning to determine pro-inflammatory macrophage activation in gastric wall of patients with diabetic gastroparesis.

Official Title
-----------------
Dynamic Positron Emission Tomography Imaging With 11C-ER176 to Delineate Macrophage Activation in Diabetic Gastroparesis

Conditions
-----------------
Diabetes, Gastroparesis With Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: PET/CT Scan with 11C-ER176
* Diagnostic Test: Core biopsy of gastric muscle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18 to 70 years of age. Ability to provide informed consent. Type I or II diabetes mellitus. Gastroparesis defined by gastric retention of Tc-99m > 60 % at 2 hrs and/or > 10% at 4 hours on scintigraphy. Average Gastroparesis Cardinal Symptom Index (GCSI) ≥ 3 indicating moderate-severe symptoms. Exclusion Criteria: Women who are pregnant or cannot stop breast feeding for 24 hours. Using anti-coagulants, anti-inflammatory medications (NSAIDs, corticosteroids, etc.) or immunosuppressive therapies within the 4 weeks prior. Opioid use within the last 4 weeks of gastric emptying scintigraphy. Prior gastric surgery. History of IBD, celiac disease, eosinophilic gastroenteritis, microscopic colitis. Healthy Subjects Exclusion criteria no clinical history of diabetes or any GI symptoms no inflammatory disorders of the GI tract no use of anti-inflammatory or immunosuppressive therapies

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Three groups of patients (diabetic; diabetic gastroparesis; healthy volunteers) will undergo PET-CT. The diabetic gastroparesis group will also undergo gastric muscle biopsy of the involved and uninvolved area to validate immune changes visualized on imaging.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diabetic Gastroparesis Subjects<br>Type I or II diabetes subjects who also have a diagnosis of Gastroparesis (defined by gastric retention of Tc-99m >20% at 4 hrs on scintigraphy). Subjects will receive PET/CT Scan with 11C-ER176 and a core biopsy of gastric muscle | Drug: PET/CT Scan with 11C-ER176<br>* Subjects will have a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh for attenuation correction (CTAC) and anatomic co-localization. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 will be administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh will then be acquired.<br>Diagnostic Test: Core biopsy of gastric muscle<br>* The echoendoscope (Aloka Arietta 850; Olympus, Center Valley, PA) will be advanced into the gastric lumen and a site targeted for EUS-guided core biopsies based on findings of the PET scan. Fine needle biopsy of the gastric wall will be performed.<br>|
| Experimental: Diabetic without gastroparesis subjects<br>Type I or II diabetes subjects who have not been clinically diagnosed with Gastroparesis. Subjects will receive PET/CT Scan with 11C-ER176 | Drug: PET/CT Scan with 11C-ER176<br>* Subjects will have a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh for attenuation correction (CTAC) and anatomic co-localization. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 will be administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh will then be acquired.<br>|
| Placebo Comparator: Healthy Subjects<br>Healthy subjects will be age-matched and receive a PET/CT Scan with 11C-ER176 | Drug: PET/CT Scan with 11C-ER176<br>* Subjects will have a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh for attenuation correction (CTAC) and anatomic co-localization. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 will be administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh will then be acquired.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of 11C-ER 176 in the Stomach Muscle | All patients will have a PET/CT with 11C-ER 176. On each PET image, volumes of interest areas will be drawn around the stomach and other organs that may show radiotracer accumulation. The uptake of radiotracer 11C-ER 176 in each area will be quantified and reported as maximum standardized uptake values (SUVmax) | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Immune Cells With CD45 Expression | An upper endoscopy procedure was done for diabetic gastroparesis patients and full thickness core tissue samples were taken in the stomach in areas that demonstrated 11C-ER 176 uptake in the PET scan as well as non-enhancing control areas. Cytometry by time of flight (CyTOF) mass spectrometry system was used to determine the proportions of immune cell types with CD45. | baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
macrophages, immune cells, gastric emptying, gastroparesis, imaging