Positron Emission Tomography (PET) Imaging of Pancreatic Beta-Cell Mass in Healthy and Type 1 Diabetic Patients

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: 18F-FP-DTBZ (18F-AV-133); Biological: Arginine-hydrochloride

• Registration Number: NCT00958997
• Lead Sponsor: Yale University

Brief Summary

Pancreatic Islet beta-cells are responsible for synthesizing and secreting appropriate amounts of insulin to regulate blood glucose levels. One factor in the development of diabetes is the loss of beta-cells. Developing treatments to prevent or restore islet beta-cell mass (BCM) in diabetic patients is hampered by a lack of methods for the non-invasive imaging of these cells. This study is designed to evaluate a radiolabeled compound that binds to the pancreatic islet. The investigators will test the ability of one promising imaging compound, 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-FP-DTBZ), to measure the amount of pancreatic islet beta-cells in patients with long-standing type-1 diabetes and in age-weight-matched healthy control subjects.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2009-08
• Study First Submitted: 2009-08-12
• Study First Submitted QC: 2009-08-13
• Study First Posted: 2009-08-14
• Primary Completion: 2011-10
• Study Completion: 2012-05
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-20
• Last Update Posted: 2012-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Patients with Type 1 diabetes may be enrolled if they meet all of the following criteria:

   • Have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician; diabetes onset younger than age 18, duration >5 years
   • Have fasting C-Peptide ≤ 0.1 ng/ml
   • BMI between 18 and 29 kg/m2
   • Able to tolerate PET and MR imaging
   • No metal implants
   • No claustrophobia

2. Healthy volunteers may be enrolled if they meeting all of the following criteria:

   • Have no history of Type 1 diabetes
   • Fasting blood glucose ≤ 100 mg/dL
   • Negative islet autoantibody testing
   • BMI between 18 and 29 kg/m2
   • Able to tolerate PET and MR imaging
   • No history of previous allergic reactions to drugs
   • No metal implants
   • No claustrophobia

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Exclusion 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;
• History of allergic reactions to any drug
• Current use of any medications except for insulin for Type 1 diabetes
• Clinically significant cardiovascular disease or clinically significant abnormalities on screening ECG (including but not limited to QTc>450 msec);
• Clinically significant psychiatric disease; 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; subjects will be asked about this. No testing will be performed.
• Have a history of alcohol or substance abuse or dependence;
• Are women of childbearing potential 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 lactating at screening, and must agree to take appropriate steps not to become pregnant during the study and for 30 days following the study.
• Currently receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days.
• Have received a diagnostic or therapeutic radiopharmaceutical within 7 days prior to participation in this study.
• Claustrophobia
• Metal implants (pace-maker, artificial joints, non-removable body piercings)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Type 1 diabetic subjects	18F-FP-DTBZ (18F-AV-133)	Patients with Type 1 diabetes who have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician
Type 1 diabetic subjects	Arginine-hydrochloride	Patients with Type 1 diabetes who have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician
Healthy control subjects	18F-FP-DTBZ (18F-AV-133)	Age-weight-BMI matched to the subjects with type-1 diabetes
Healthy control subjects	Arginine-hydrochloride	Age-weight-BMI matched to the subjects with type-1 diabetes

Primary Outcome Measures

Name	Time	Method
PET-determined pancreatic islet beta-cell mass	150 minutes post-dose of imaging agent

Secondary Outcome Measures

Name	Time	Method
Insulin secretion response following an acute arginine-stimulus test	Six minutes following administration of arginine challange

Trial Locations

Locations (1)

Yale University School of Medicine, PET Center; 🇺🇸 New Haven, Connecticut, United States