A Trial of 18F-AV-133 Positron Emission Tomography (PET)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and pancreas imaging properties of 18F-AV-133.

Detailed Description
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The primary objective of this protocol is to address the feasibility for further development of the VMAT2-binding compound 18F-AV-133 as a diagnostic radiopharmaceutical in the field of diabetes. Specifically, this study will evaluate 18F-AV-133 imaging in patients with type 1 diabetes, patients with type 2 diabetes and in healthy controls in order to: Obtain information regarding the safety of 18F-AV-133 in these populations; Determine whether uptake, distribution, or clearance of 18F-AV-133 in the pancreas differs between subjects with predicted reduced beta cell mass (patients with type 1 or type 2 diabetes of long duration) and normal beta cell mass (healthy volunteers); Evaluate the PET imaging pharmacokinetics of 18F-AV-133 in abdominal organs of healthy control subjects and patients with type 1 or type 2 diabetes; Obtain preliminary information regarding the appropriate time window for optimal PET imaging of 18F-AV-133 in the pancreas post-administration for type 1, type 2, and normal healthy individuals; Obtain preliminary information regarding an appropriate reference tissue for evaluating the PET imaging results of 18F-AV-133 in the pancreas; and Evaluate the imaging properties of 18F-AV-133 in the pancreas relative to the brain in a subset of subjects.

Official Title
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A Preliminary Evaluation of the Safety and Pancreas Imaging Properties of 18F-AV-133 in Healthy Volunteers and in Patients With Type 1 or Type 2 Diabetes

Conditions
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Type 1 Diabetes, Type 2 Diabetes

Intervention / Treatment
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* Drug: 18F-AV-133


Participation Criteria
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Eligibility Criteria
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Patients with type 1 diabetes may be enrolled if they meet all of the following criteria: Are males or females between 18 and 70 years of age, inclusive; Have a diagnosis of type 1 diabetes mellitus as defined by ADA criteria; diabetes onset younger than age 21, duration >5 years; Insulin dose requirements ≤ 0.8 units/kg/day; HbA1c level ≥ 5% and ≤ 8%; Have fasting C-Peptide < 0.1 ng/ml; Have a BMI between 18 and 32 kg/m2; Able to tolerate PET imaging; In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and Give informed consent. Patients with type 2 diabetes may be enrolled if they meet all of the following criteria: Are males or females between 18 and 70 years of age, inclusive; Must have been diagnosed with type 2 diabetes for more than five years; HbA1c level ≥ 5% and ≤ 8%; Have a BMI between 18 and 32 kg/m2; Glucose > 200 mg/dl on Mixed Meal Tolerance Test at screening visit; Able to tolerate PET imaging; In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and Give informed consent. Healthy volunteers may be enrolled if they meet all of the following criteria: Are males or females between 18 and 70 years of age, inclusive; Have no history of type 1 or type 2 diabetes in a first degree relative; Fasting blood glucose ≤ 100 mg/dL; HbA1c level ≤ 6%; Normal Mixed Meal Tolerance test at screening visit; BMI between 18 and 32 kg/m2; Able to tolerate PET imaging; In the judgment of the physician, are capable of fasting 4-6 hours prior to screening and Day 1 imaging procedures; and Give informed consent. Subjects will be excluded from enrollment if they meet any of the following criteria: Clinically significant renal dysfunction; Clinically significant liver dysfunction as determined by history, physical examination, and standard liver function testing at screening (AST, ALT, Total/Direct Bilirubin, Alkaline Phosphatase); Coagulopathy; Use medications known to affect dopaminergic function, including MAO inhibitors, tetrabenazine, or levodopa; Recent (within 3 months) or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. glucocorticoids, reserpine); Have polycystic ovarian syndrome; History of movement disorder such as Parkinson's Disease, Huntington's Disease; Clinically significant psychiatric disease or history of psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia; Current use (within past year) of cocaine, methamphetamine, and/or ecstasy ( MDMA, 34- methylenedioxymethamphetamine; Have a recent history of alcohol or substance abuse or dependence; Clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG (including but not limited to QTc>450 msec); Clinically significant pulmonary, renal or hepatic impairment, or cancer; Have clinically significant infectious disease, including AIDS or HIV infection or previous positive test for hepatitis B, hepatitis C, HIV-1, or HIV-2; Are women of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using adequate contraception. Women must not be pregnant (negative serum β-HCG at the time of screen) or breastfeeding at screening, and must agree to take appropriate steps not to become pregnant for 30 days following the clinical trial; Require medications with a narrow therapeutic window (e.g., warfarin), are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days; Weigh more than the manufacturer-recommended limit for the PET/CT camera being used; Any prior participation in other research protocols within the past month that involved radiation, with the exception of plain radiography studies (i.e., chest x-rays); and Have received a diagnostic or therapeutic radiopharmaceutical within the past week.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Type 1 Diabetes<br> | Drug: 18F-AV-133<br>* IV injection, 7.6 mCi (281.2 MBq)<br>|
| Experimental: Type 2 Diabetes<br> | Drug: 18F-AV-133<br>* IV injection, 7.6 mCi (281.2 MBq)<br>|
| Experimental: Healthy Controls<br> | Drug: 18F-AV-133<br>* IV injection, 7.6 mCi (281.2 MBq)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreatic uptake and clearance of 18F-AV-133 tracer as determined by SUVR | SUVR=standard uptake value ratio | 0-90 minutes |