Quantitative 18F-AV-133 PET Imaging in Subjects With Diabetes and Healthy Controls

Study Overview
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Brief Summary
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To evaluate 18F-AV-133 imaging of the pancreas in patients with early type 2 diabetes, late type 2 diabetes, subjects with pre-diabetes and in healthy overweight/obese control subjects. These subjects will also be evaluated for beta-cell function as measured by the insulin and C-peptide response to a challenge with intravenous arginine under basal and glucose enhanced conditions.

Official Title
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Quantitative PET Imaging of Pancreatic Beta-Cell Mass in Healthy Overweight/Obese Subjects, Subjects With Prediabetes, and Type 2 Diabetes Patients With 18F-FP-DTBZ (18F-AV-133)

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: 18F-AV-133
* Drug: 10% Arginine Hydrochloride-R-Gene 10


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female subjects of non-childbearing potential between the ages of 30 and 65 years inclusive. Able to tolerate PET, PET/CT and MR imaging Estimated creatinine clearance >= 60mL/min Informed consent documents signed and dated by subject Subjects must be willing and able to comply with all scheduled visits, treatments laboratory tests, scans and other study procedures. In addition, subjects must meet classification requirements for one of the following Healthy Overweight Pre-diabetes T2DM (T2DM only) Subjects with other chronic medical conditions (besides diabetes) that are well controlled and stable on medication are acceptable for inclusion in this study. Exclusion Criteria: Subjects who are affiliated with or relatives of staff members of either the site or Pfizer directly involved in the conduct of the trial. Conditions which in the opinion of the study investigator may interfere with the subject's ability to participate in the study History of allergic reaction to drug/contrast agent or history of drug/alcohol abuse Subjects who have received investigational medications within the last 30 days or a radiopharmaceutical in the past 7 days. Pregnant or nursing females; females of childbearing potential.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arginine Stimulation Testing<br>Establish the methodology for glucose enhanced arginine stimulation testing (AST). | Drug: 10% Arginine Hydrochloride-R-Gene 10<br> <br> |
| Experimental: PET Imaging<br>Determine if pancreatic PET-determined binding measures of 18F-AV-133 differ in up to 60 subjects determined to be at one of four stages of the natural history of Type 2 Diabetes: Healthy Overweight/obese Volunteers (HOV), Subjects with Pre-diabetes (PD) and Type 2 Diabetes mellitus (T2DM). | Drug: 18F-AV-133<br>* 296 MBq (8 mCi)<br>Drug: 10% Arginine Hydrochloride-R-Gene 10<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal PET-determined mean pancreatic Binding Potential of 18F-AV-133 |  | PET visit 1 | 
| Optimal PET-determined mean pancreatic Standardized Uptake Value (SUV) of 18F-AV-133 |  | PET visit 1 | 
| Optimal PET-determined mean pancreatic Volume of Distribution (VT) of 18F-AV-133 |  | PET visit 1 |