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

NCT00958997 | Completed

• 1 other identifier: Y-003-09
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

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

Outcome Measures

Primary Outcomes (1)

• PET-determined pancreatic islet beta-cell mass

  150 minutes post-dose of imaging agent

Secondary Outcomes (1)

• Insulin secretion response following an acute arginine-stimulus test

  Six minutes following administration of arginine challange

Study Arms (2)

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); Biological: Arginine-hydrochloride

Healthy control subjects

Age-weight-BMI matched to the subjects with type-1 diabetes

Drug: 18F-FP-DTBZ (18F-AV-133); Biological: Arginine-hydrochloride

Interventions

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

Healthy control subjects; Type 1 diabetic subjects

Arginine-hydrochloride BIOLOGICAL

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

Healthy control subjects; Type 1 diabetic subjects

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Yale University: lead
• Pfizer: collaborator
• Avid Radiopharmaceuticals: collaborator

Study Sites (1)

Yale University School of Medicine, PET Center

New Haven, Connecticut, 06520, United States

Location

Related Publications (7)

• 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.

  PMID: 16934687 BACKGROUND

• 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.

  PMID: 17383572 BACKGROUND

• 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.

  PMID: 17383573 BACKGROUND

• 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.

  PMID: 18552132 BACKGROUND

• 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.

  PMID: 9686917 BACKGROUND

• 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.

  PMID: 18049122 BACKGROUND

• 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.

  PMID: 16710474 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

florbenazine F 18; Arginine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Gary W Cline, Ph.D.

  Yale University

  PRINCIPAL INVESTIGATOR

• Yu-Shin Ding, Ph.D.

  Yale University

  STUDY DIRECTOR

• Kitt F Petersen, M.D.

  Yale University

  STUDY DIRECTOR

• Richard Carson, Ph.D.

  Yale University

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 12, 2009
• First Posted: August 14, 2009
• Study Start: August 1, 2009
• Primary Completion: October 1, 2011
• Study Completion: May 1, 2012
• Last Updated: July 23, 2012

Record last verified: 2012-07

Locations

US (1)