Evaluation of 18 F-FP-DTBZ Pancreatic PET Scanning as a Tool to Measure Beta Cell Mass

NCT02236754 | Completed Early Phase 1 Results DMC

• 2 other identifiers: AAAJ5709R01DK077493-03
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes mellitus (T1DM) develops when there is impaired insulin production due to loss of insulin producing cells (beta cells). The amount of insulin that can be produced is imperfectly correlated with beta cell mass (BCM). The development of a reliable method to noninvasively quantify the total amount of insulin producing beta cells would be of great benefit by providing an important endpoint for the development of new treatments of diabetes. The investigators have previously identified a specific marker on islet cells called vesicular monoamine transporter 2 (VMAT2) that the investigators now propose to use in positron emission tomography (PET) scanning to determine islet beta cell mass. The PET radiopharmaceutical 18 F-fluoropropyl(FP)-dihydrotetrabenazine(DTBZ) has been used previously in human subjects without adverse effects. It has shown promise in differentiating type 1 diabetes and non-diabetes. The investigators now hypothesize that repeat PET scans will be reproducible in the same subject. Subjects with normal BCM will be recruited from among normal weight non-diabetic people with plasma insulin levels within the normal range. Subjects with predicted reduced BCM will be recruited from among patients with T1DM who have low or non-measurable insulin levels. Two PET scan measurements will be taken in each subject and the amount of VMAT2 in the pancreas will be and compared for reproducible findings. Biochemical testing will also be performed and compared to PET scans as a potential indirect marker of beta cell mass.

Conditions

Healthy Volunteers; Diabetes Mellitus, Type 1

Keywords

dihydrotetrabenazine; beta cell mass; diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• Mean VMAT2 Functional Binding Capacity in the β Cells to 18 F-FP-DTBZ

  The VMAT2 functional binding capacity in the body and tail of the pancreas is calculated as BPND (VMAT2 binding potential) × PET ROI (region-of-interest) Volume. BPND is unitless, and ROI unit is mL. Higher values of the VMAT functional binding capacity indicates greater β cell mass.

  Up to 2 months from enrollment

Study Arms (2)

Healthy Controls

OTHER

Pancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in healthy controls: subjects with predicted normal BCM (healthy, normal weight, non-diabetic individuals who have stimulated insulin and c-peptide levels within the normal range).

Drug: 18 F-FP-DTBZ; Radiation: PET Scanning

Patients with T1D

OTHER

Pancreatic 18 F-FP-DTBZ uptake will be measured with PET scanning in patients with longstanding T1D: subjects with predicted reduced beta cell mass (subjects with established T1DM who have low or no measurable stimulated insulin and c-peptide levels).

Drug: 18 F-FP-DTBZ; Radiation: PET Scanning

Interventions

18 F-FP-DTBZ DRUG

The drug, no carrier added \[18 F\]-FP-DTBZ, is formulated in 5% (v/v) ethanol in 0.9% sterile saline solution to produce \[18 F\]-FP-DTBZ for injection. Subjects will receive a single i.v. administration of no more than 7.6 millicuries (mCi) of \[18 F\]-FP-DTBZ for injection immediately prior to imaging. The specific activity at time of injection will less than 1.0 mCi/microgram and thus for a 7.6 mCi dose the maximal mass dose will be less than 10 microgram.

Healthy Controls; Patients with T1D

PET Scanning RADIATION

Individuals will be imaged continuously (i.e. dynamically) for 2 hours.

Also known as: Positron Emission Tomography

Healthy Controls; Patients with T1D

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 1 diabetes may be enrolled if they meet all of the following criteria:
• Are males or females between 18 and 70 years of age, inclusive
• Have a diagnosis of type 1 diabetes mellitus as defined by the American Diabetes Association (ADA) criteria or by diagnosed as per their endocrinologist; duration \>5 years; Insulin dose requirements \<0.8 units/kg/day
• HbA1c level between 5% and 8.5%
• Have fasting C-Peptide \< 0.1 ng/ml
• Have a body mass index (BMI) between 18 and 32 kg/m2
• Able to tolerate PET imaging
• In the judgment of the physician, are capable of fasting 4 to 6 hours prior to screening and Day 1 imaging procedures
• Give informed consent
• Healthy volunteers may be enrolled if they meeting all of the following criteria:
• Are males or females between 18 and 70 years of age, inclusive
• Have no history of type 1 or type 2 diabetes in a first degree relative
• Fasting blood glucose less than 100 mg/dL
• HbA1c level less than 6%
• Normal Mixed Meal Tolerance test at screening visit

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 (aspartate aminotransferase (AST), alanine aminotransferase (ALT), Total/Direct Bilirubin, Alkaline Phosphatase)
• Coagulopathy
• Use medications known to affect dopaminergic function, including monoamine oxidase (MAO) inhibitors, tetrabenazine, or levodopa
• Recent (within 3 months) or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. glucocorticoids, reserpine) medications known to affect dopaminergic function, including MAO inhibitors, tetrabenazine, or levodopa
• Have polycystic ovarian syndrome
• History of movement disorder such as Parkinson's Disease, Huntington's Disease
• Clinically significant psychiatric disease or history of psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia
• Current use (within past year) of cocaine, methamphetamine, and/or ecstasy (3,4methylenedioxymethamphetamine (MDMA))
• Have a recent history of alcohol or substance abuse or dependence
• Clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (ECG) (including but not limited to QT-interval time corrected \> 450 msec)
• Clinically significant pulmonary, renal or hepatic impairment, or cancer
• Have clinically significant infectious disease, including acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection or previous positive test for hepatitis B, hepatitis C, or HIV.
• Are women of childbearing potential not refraining from sexual activity or not using adequate contraception.
• Women must not be pregnant (negative serum human chorionic gonadotropin (hCG) at the time of screen) or breastfeeding at screening, and must agree to take appropriate steps not to become pregnant during for 30 days following the clinical trial

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Naomi Berrie Diabetes Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE. 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. doi: 10.2967/jnumed.108.054866. Epub 2009 Feb 17.

  PMID: 19223416 BACKGROUND

• Freeby MJ, Kringas P, Goland RS, Leibel RL, Maffei A, Divgi C, Ichise M, Harris PE. Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for beta Cell Mass Estimates in Diabetes. Mol Imaging Biol. 2016 Apr;18(2):292-301. doi: 10.1007/s11307-015-0888-7. Epub 2015 Sep 14.

  PMID: 26370678 RESULT

Related Links

• Investigator web site

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus

Interventions

florbenazine F 18; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Dr. Paul Harris
• Organization: Columbia University

peh1@cumc.columbia.edu

212-305-7363

Study Officials

• Paul Harris, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: September 11, 2014
• Study Start: July 2, 2013
• Primary Completion: April 23, 2014
• Study Completion: April 23, 2014
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2024-07

Locations

US (1)