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

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

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

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes; Type 2 Diabetes
• Intervention / Treatment: Drug: 18F-AV-133

Detailed Description

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:

1. Obtain information regarding the safety of 18F-AV-133 in these populations;
2. 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);
3. 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;
4. 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;
5. Obtain preliminary information regarding an appropriate reference tissue for evaluating the PET imaging results of 18F-AV-133 in the pancreas; and
6. Evaluate the imaging properties of 18F-AV-133 in the pancreas relative to the brain in a subset of subjects.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10027
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Avid Radiopharmaceuticals

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: February 21, 2011
• First Submitted That Met QC Criteria: January 18, 2012
• First Posted (Estimate): January 24, 2012

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 18F-AV-133-D01