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

NCT ID: NCT00958997

Last Updated: 2012-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

16 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-08-31

Study Completion Date

2012-05-31

Brief Summary

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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

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Conditions

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Diabetes Mellitus, Type 1

Keywords

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diabetes islet pancreas beta cell mass PET imaging FPDTBZ arginine stimulus test

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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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

18F-FP-DTBZ (18F-AV-133)

Intervention Type DRUG

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).

Arginine-hydrochloride

Intervention Type BIOLOGICAL

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

18F-FP-DTBZ (18F-AV-133)

Intervention Type DRUG

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).

Arginine-hydrochloride

Intervention Type BIOLOGICAL

A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.

Interventions

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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).

Intervention Type DRUG

Arginine-hydrochloride

A bolus injection of 5g of 10% arginine-hydrochloride will be given over a period of 1 minute.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Avid Radiopharmaceuticals

INDUSTRY

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role lead

Responsible Party

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Gary Cline

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gary W Cline, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Yu-Shin Ding, Ph.D.

Role: STUDY_DIRECTOR

Yale University

Kitt F Petersen, M.D.

Role: STUDY_DIRECTOR

Yale University

Richard Carson, Ph.D.

Role: STUDY_DIRECTOR

Yale University

Locations

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Yale University School of Medicine, PET Center

New Haven, Connecticut, United States

Site Status

Countries

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United States

References

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Goswami R, Ponde DE, Kung MP, Hou C, Kilbourn MR, Kung HF. Fluoroalkyl derivatives of dihydrotetrabenazine as positron emission tomography imaging agents targeting vesicular monoamine transporters. Nucl Med Biol. 2006 Aug;33(6):685-94. doi: 10.1016/j.nucmedbio.2006.05.006.

Reference Type BACKGROUND
PMID: 16934687 (View on PubMed)

Kilbourn MR, Hockley B, Lee L, Hou C, Goswami R, Ponde DE, Kung MP, Kung HF. Pharmacokinetics of [(18)F]fluoroalkyl derivatives of dihydrotetrabenazine in rat and monkey brain. Nucl Med Biol. 2007 Apr;34(3):233-7. doi: 10.1016/j.nucmedbio.2007.01.007.

Reference Type BACKGROUND
PMID: 17383572 (View on PubMed)

Kung MP, Hou C, Goswami R, Ponde DE, Kilbourn MR, Kung HF. Characterization of optically resolved 9-fluoropropyl-dihydrotetrabenazine as a potential PET imaging agent targeting vesicular monoamine transporters. Nucl Med Biol. 2007 Apr;34(3):239-46. doi: 10.1016/j.nucmedbio.2006.12.005.

Reference Type BACKGROUND
PMID: 17383573 (View on PubMed)

Kung MP, Hou C, Lieberman BP, Oya S, Ponde DE, Blankemeyer E, Skovronsky D, Kilbourn MR, Kung HF. In vivo imaging of beta-cell mass in rats using 18F-FP-(+)-DTBZ: a potential PET ligand for studying diabetes mellitus. J Nucl Med. 2008 Jul;49(7):1171-6. doi: 10.2967/jnumed.108.051680. Epub 2008 Jun 13.

Reference Type BACKGROUND
PMID: 18552132 (View on PubMed)

Larsson H, Ahren B. Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine. Diabetologia. 1998 Jul;41(7):772-7. doi: 10.1007/s001250050986.

Reference Type BACKGROUND
PMID: 9686917 (View on PubMed)

Rickels MR, Naji A, Teff KL. Acute insulin responses to glucose and arginine as predictors of beta-cell secretory capacity in human islet transplantation. Transplantation. 2007 Nov 27;84(10):1357-60. doi: 10.1097/01.tp.0000287595.16442.a7.

Reference Type BACKGROUND
PMID: 18049122 (View on PubMed)

Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE. Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest. 2006 Jun;116(6):1506-13. doi: 10.1172/JCI27645. Epub 2006 May 18.

Reference Type BACKGROUND
PMID: 16710474 (View on PubMed)

Other Identifiers

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Y-003-09

Identifier Type: -

Identifier Source: org_study_id