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

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Avid Radiopharmaceuticals
Information provided by (Responsible Party):
Gary Cline, Yale University
ClinicalTrials.gov Identifier:
NCT00958997
First received: August 12, 2009
Last updated: July 20, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention
Diabetes Mellitus, Type 1
Drug: 18F-FP-DTBZ (18F-AV-133)
Biological: Arginine-hydrochloride

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Quantitative PET Imaging of Pancreatic Beta-cell Mass in Healthy and Type 1 Diabetic Patients With 18F-FP-DTBZ (AV-133)

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • PET-determined pancreatic islet beta-cell mass [ Time Frame: 150 minutes post-dose of imaging agent ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Insulin secretion response following an acute arginine-stimulus test [ Time Frame: Six minutes following administration of arginine challange ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood plasma


Enrollment: 16
Study Start Date: August 2009
Study Completion Date: May 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Type 1 diabetic subjects
Patients with Type 1 diabetes who have a diagnosis of Type 1 diabetes mellitus defined by ADA criteria or judgment of physician
Drug: 18F-FP-DTBZ (18F-AV-133)
The subjects will receive a single IV bolus of approximately 10 mCi 18F-AV-133.(Injection will contain no more than 25 µg of non-radiolabeled 19F-AV-133).
Biological: Arginine-hydrochloride
A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.
Healthy control subjects
Age-weight-BMI matched to the subjects with type-1 diabetes
Drug: 18F-FP-DTBZ (18F-AV-133)
The subjects will receive a single IV bolus of approximately 10 mCi 18F-AV-133.(Injection will contain no more than 25 µg of non-radiolabeled 19F-AV-133).
Biological: Arginine-hydrochloride
A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Community Sample

Criteria

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

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00958997

Locations
United States, Connecticut
Yale University School of Medicine, PET Center
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Pfizer
Avid Radiopharmaceuticals
Investigators
Principal Investigator: Gary W Cline, Ph.D. Yale School of Medicine
Study Director: Yu-Shin Ding, Ph.D. Yale School of Medicine
Study Director: Kitt F Petersen, M.D. Yale School of Medicine
Study Director: Richard Carson, Ph.D. Yale School of Medicine
  More Information

Publications:

Responsible Party: Gary Cline, Associate Professor, Yale University
ClinicalTrials.gov Identifier: NCT00958997     History of Changes
Other Study ID Numbers: Y-003-09
Study First Received: August 12, 2009
Last Updated: July 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
diabetes
islet
pancreas
beta cell mass
PET imaging
FPDTBZ
arginine stimulus test

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 29, 2014