Diabetes, Gastroparesis With Diabetes Mellitus
Conditions
Keywords
macrophages, immune cells, gastric emptying, gastroparesis, imaging
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.
Interventions
DRUGPET/CT Scan with 11C-ER176
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.
DIAGNOSTIC_TESTCore biopsy of gastric muscle
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.
Sponsors
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
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. Healthy Subjects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Uptake of 11C-ER 176 in the Stomach Muscle | baseline | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Immune Cells With CD45 Expression | baseline | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diabetic Gastroparesis Subjects 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), received a PET/CT scan with 11C-ER176 and a core biopsy of gastric muscle.
PET/CT scan with 11C-ER176: Subjects received a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 was administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh was then acquired.
Core biopsy of gastric muscle: The echoendoscope (Aloka Arietta 850; Olympus, Center Valley, PA) was 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 was performed. | 4 |
| Diabetic Without Gastroparesis Subjects Type I or II diabetes subjects who have not been clinically diagnosed with Gastroparesis. Subjects received a PET/CT scan with 11C-ER176.
PET/CT scan with 11C-ER176: Subjects received a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 was administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh was then acquired. | 4 |
| Healthy Subjects Healthy subjects were age-matched and received a PET/CT scan with 11C-ER176.
PET/CT scan with 11C-ER176: Subjects received a low-dose, non-gated, non-contrast-enhanced, free-breathing CT from the orbits to upper thigh. Immediately following the start of the PET scan, 518 MBq (14 mCi) (range 370-666 MBq; 10-18 mCi) of 11C-ER 176 was administered intravenously followed by a saline flush. A whole-body PET scan from the orbits to upper thigh was then acquired. | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Diabetic Gastroparesis Subjects | Total | Healthy Subjects | Diabetic Without Gastroparesis Subjects |
|---|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 7 | 48.0 years STANDARD_DEVIATION 10 | 47.0 years STANDARD_DEVIATION 11 | 48.0 years STANDARD_DEVIATION 13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 11 Participants | 4 Participants | 4 Participants |
| Region of Enrollment United States | 4 participants | 12 participants | 4 participants | 4 participants |
| Sex: Female, Male Female | 4 Participants | 12 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 4 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
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)
Time frame: baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Diabetic Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach pylorus | 5.5 SUVmax | Standard Deviation 1 |
| Diabetic Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach gastric fundus | 7.8 SUVmax | Standard Deviation 1.9 |
| Diabetic Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach body | 7.8 SUVmax | Standard Deviation 1.9 |
| Diabetic Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | duodenum | 7.0 SUVmax | Standard Deviation 1.8 |
| Diabetic Without Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | duodenum | 9.5 SUVmax | Standard Deviation 6.8 |
| Diabetic Without Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach pylorus | 8.4 SUVmax | Standard Deviation 4.1 |
| Diabetic Without Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach body | 13.0 SUVmax | Standard Deviation 9.2 |
| Diabetic Without Gastroparesis Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach gastric fundus | 13.1 SUVmax | Standard Deviation 8.3 |
| Healthy Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | duodenum | 6.2 SUVmax | Standard Deviation 2.1 |
| Healthy Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach gastric fundus | 9.0 SUVmax | Standard Deviation 1.6 |
| Healthy Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach body | 7.7 SUVmax | Standard Deviation 1.9 |
| Healthy Subjects | Uptake of 11C-ER 176 in the Stomach Muscle | stomach pylorus | 4.6 SUVmax | Standard Deviation 0.2 |
Secondary
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.
Time frame: baseline
Population: The tissue obtained from diabetic gastroparesis group was not of sufficient size or volume to perform quantitative (%) assessment. Outcome measure for diabetic gastroparesis subjects only.