PET Imaging to Delineate Macrophage Activation in Diabetic Gastroparesis

Sponsor

Mayo Clinic (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04762719

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arm

33.7

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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. This study aims 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Gastroparesis With Diabetes Mellitus	Drug: PET/CT Scan with 11C-ER176 Diagnostic Test: Core biopsy of gastric muscle	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

May 10, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: PET/CT Scan with 11C-ER176	Drug: PET/CT Scan with 11C-ER176 An enrichment of markers associated with pro-inflammatory macrophages as well as loss of anti-inflammatory macrophages has been demonstrated in gastroparesis. There are currently no non-invasive ways of assessing immunopathology in the gastric muscle. Additionally, cellular changes can be patchy and untargeted full-thickness biopsies do not allow a comprehensive assessment of the gastric wall. Recently, there have been advancements in radioligands that can be used to determine activated macrophages. A novel, third-generation translocator protein (TSPO)-specific radioligand is ER176, which has shown high affinity and excellent in vivo target-to-background binding. Our preliminary data shows that TSPO is expressed in human gastric muscle macrophages. The overall goal of this proposal is to determine the utility of 11C-ER176 PET/CT imaging for assessing macrophage activation in vivo in gastric muscle of patients with diabetic gastroparesis. Diagnostic Test: Core biopsy of gastric muscle We hypothesize that increased uptake of 11C-ER176 associates with a shift towards pro-inflammatory macrophage milieu on tissue assessment made by targeted biopsies of gastric muscle. EUS guided biopsies will be taken from the enhancing as well as non-enhancing (control) areas from the diabetic gastroparesis patients. Immune cell gene expression will be determined for pro- and anti-inflammatory gene markers

Arm

Intervention/Treatment

Other: PET/CT Scan with 11C-ER176

Drug: PET/CT Scan with 11C-ER176

An enrichment of markers associated with pro-inflammatory macrophages as well as loss of anti-inflammatory macrophages has been demonstrated in gastroparesis. There are currently no non-invasive ways of assessing immunopathology in the gastric muscle. Additionally, cellular changes can be patchy and untargeted full-thickness biopsies do not allow a comprehensive assessment of the gastric wall. Recently, there have been advancements in radioligands that can be used to determine activated macrophages. A novel, third-generation translocator protein (TSPO)-specific radioligand is ER176, which has shown high affinity and excellent in vivo target-to-background binding. Our preliminary data shows that TSPO is expressed in human gastric muscle macrophages. The overall goal of this proposal is to determine the utility of 11C-ER176 PET/CT imaging for assessing macrophage activation in vivo in gastric muscle of patients with diabetic gastroparesis.

Diagnostic Test: Core biopsy of gastric muscle

We hypothesize that increased uptake of 11C-ER176 associates with a shift towards pro-inflammatory macrophage milieu on tissue assessment made by targeted biopsies of gastric muscle. EUS guided biopsies will be taken from the enhancing as well as non-enhancing (control) areas from the diabetic gastroparesis patients. Immune cell gene expression will be determined for pro- and anti-inflammatory gene markers

Outcome Measures

Primary Outcome Measures

Quantification of uptake and distribution of 11C-ER 176 in the stomach muscle between patients with diabetic gastroparesis and controls (diabetic without gastroparesis and non-diabetic). [Through study completion, an average of 1 year]
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.

Secondary Outcome Measures

Assessment of gastric macrophages in diabetic gastroparesis patients. [Through study completion, an average of 1 year]
An upper endoscopy procedure will be done for diabetic gastroparesis patients and full thickness core tissue samples will be taken in the stomach in areas that demonstrated 11C-ER 176 uptake in the PET scan as well as non-enhancing control areas. Immune cells will be assessed to determine expression of key pro and anti-inflammatory immune markers.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

Principal Investigator: Madhusudan Grover, MBBS, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

Madhusudan (Madhu) Grover, MBBS, Principal Investigator, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT04762719

Other Study ID Numbers:

20-010260

First Posted:

Feb 21, 2021

Last Update Posted:

Apr 12, 2022

Last Verified:

Apr 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Madhusudan (Madhu) Grover, MBBS, Principal Investigator, Mayo Clinic

macrophages, immune cells, gastric emptying, gastroparesis, imaging

Additional relevant MeSH terms:

Gastroparesis

Diabetes Mellitus

Study Results

No Results Posted as of Apr 12, 2022