Clinical trial NCT00958997: Positron Emission Tomography (PET) Imaging of Pancreatic Beta-Cell Mass in Healthy and Type 1 Diabetic Patients
Official title: Quantitative PET Imaging of Pancreatic Beta-cell Mass in Healthy and Type 1 Diabetic Patients With 18F-FP-DTBZ (AV-133)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 1
Keywords: diabetes
islet
pancreas
beta cell mass
PET imaging
FPDTBZ
arginine stimulus test
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Avid Radiopharmaceuticals
First posted: 2009-08-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community Sample

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.


Eligibility 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)

Primary outcomes:
measure: PET-determined pancreatic islet beta-cell mass
timeFrame: 150 minutes post-dose of imaging agent
Secondary outcomes:
measure: Insulin secretion response following an acute arginine-stimulus test
timeFrame: Six minutes following administration of arginine challange
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine, PET Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Gary W Cline, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Yu-Shin Ding, Ph.D.
role: STUDY_DIRECTOR
affiliation: Yale University
name: Kitt F Petersen, M.D.
role: STUDY_DIRECTOR
affiliation: Yale University
name: Richard Carson, Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.