Assessment of Beta Cell Mass in Type 1 Diabetes With 11C-Dihydrotetrabenazine and PET Scan

2014-08-27 03:43:31 | BioPortfolio


This study will test dihydrotetrabenazine, or 11C-DTBZ, a radioactive tracer, as an imaging agent in positron emission tomography (PET). That tracer may have the ability to noninvasively measure beta cell, that is, -cell mass (BCM) in humans. For researchers hoping to develop new treatments for diabetes mellitus, a method of measuring BCM is very important. In this study, researchers will determine if patients with Type 1 diabetes mellitus, who have almost no BCM, have much less pancreatic uptake of the tracer than do patients without diabetes. Patients ages 18 and older may be eligible for this study. Three groups will be studied: Participants who have Type 1 diabetes, those without diabetes, and those who have been successfully treated with a transplant of the pancreas or pancreas and kidney

The study involves three sets of tests that can be done as an outpatient or after being admitted to the hospital. Patients will undergo a medical history and procedures including collection of blood (about 4 teaspoons), pregnancy test for women of childbearing age, magnetic resonance imaging (MRI) scan, PET scan, and tests involving arginine and glucose. Arginine is a substance that stimulates insulin release from the -cells. During the procedure, two intravenous (IV) lines are placed into the arms, one to administer arginine and the other to draw blood (about eight samples during 10 minutes). For the glucose test, patients will drink a solution of dextrose, a sugar, and blood samples will be taken over 2 hours from the IV lines. Some patients experience nausea after drinking the solution. Within 48 hours of either test or both, patients will be placed in the PET scan machine and given an injection of the radioactive material through an IV line. Blood samples of about one-half teaspoon will be drawn before the procedure starts and again every 10 seconds for the first 2 minutes and at several intervals, up to 60 minutes. Finally, patients will also an MRI scan, 30 to 60 minutes long, of the abdomen. This test will be down within two weeks of the PET scan. MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. During the scan, patients will be asked to lie still on a table that slides into the tunnel of the scanner. They will be given earplugs, for the machine can be noisy. Patients who have metal within their body that is not compatible with the MRI machine will be withdrawn from the study.


Diabetes is a metabolic disorder in which pancreatic insulin producing B-cells (located in cell clusters called the islets of Langerhans) no longer produce sufficient insulin to maintain an individual's blood sugar concentration within the normal range. Insufficient B-cell function can be caused by an autoimmune killing of the B-cells in type 1 diabetes mellitus (T1DM), or by poorly understood mechanisms in type 2 diabetes mellitus (T2DM). Regardless of the underlying cause, the development of new diabetes treatments is limited by our current inability to objectively measure B-cell mass.

We propose testing a previously used clinical radioligand, dihydrotetrabenazine (DTBZ), as a Positron Emission Tomography (PET) imaging agent for its ability to non-invasively measure B-cell mass in humans. We will study 30 patients, 10 with T1DM, 10 with normal glucose homeostasis, and 5 with a history of T1DM, but successfully restored glucose homeostasis following whole pancreas transplantation. Prior to the PET scans, each patient will undergo metabolic testing to characterize their glucose homeostasis and insulin producing capacity. The pancreas will be initially identified in each patient with high-resolution magnetic resonance imaging (MRI). Then, using anatomical landmarks identified by the MRI, the subject will undergo DTBZ-PET imaging. We predict that the radioactivity signal in the pancreas from the DTBZ-PET images will be significantly different between control subjects and T1DM subjects. Further, we predict that the DTBZ-PET images obtained in individuals with functioning pancreas allografts (and such patients have two pancreases- their native pancreas and their pancreas allografts) will reveal signal intensities from the two glands that correlates closely with each gland's insulin producing capacity. Should these studies suggest DTBZ has merit as a beta cell imaging agent, we will expand the study to include patients with T2DM.

Study Design



Type I Diabetes


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:43:31-0400

Clinical Trials [4165 Associated Clinical Trials listed on BioPortfolio]

Cohort Study of Patients With Type 1 Diabetes

This study aims to clarify the underlying hereditary and autoimmune factors that contribute to clinical type 1 diabetes and gain a better understanding of the natural history of the diseas...

Electrocardiographic Modifications and Spontaneous Hypoglycemic Episodes in Type 1 Diabetes

The population of type 1 diabetes patients with cardiovascular disease is increasing and this study aims to explore the electrocardiographic changes that are associated with spontaneous hy...

Implementation of A Patient Centered Self-Management Program for Patients With Type 2 Diabetes

Translational study based on the American Association of Diabetes Educators 7 behaviors to manage Type 2 diabetes

ECG Changes Including QT Dispersion and Corrected QT Prolongation in Children and Adolescents With Type 1 Diabetes

Diabetes Mellitus type 1 is characterized by an absolute insulin deficiency caused by T-cell-mediated autoimmune destruction of pancreatic β-cells . It is the predominant form of diabetes...

Estrogen and Diabetes

Diabetes has recently been referred to as "the epidemic of the 21st century". The reason why women with type 1 diabetes have a 2-3 fold greater risk of cardiovascular disease (CVD) compare...

PubMed Articles [9210 Associated PubMed Articles listed on BioPortfolio]

Association of Gestational Diabetes and Type 2 Diabetes Exposure In Utero With the Development of Type 2 Diabetes in First Nations and Non-First Nations Offspring.

Type 2 diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 diabetes is important to address the intergenerational bu...

The discovery of novel predictive biomarkers and early-stage pathophysiology for the transition from gestational diabetes to type 2 diabetes.

Gestational diabetes mellitus (GDM) affects up to 20% of pregnancies, and almost half of the women affected progress to type 2 diabetes later in life, making GDM the most significant risk factor for t...

Treatment of type 2 diabetes: future approaches.

Type 2 diabetes, which accounts for ~90% of all diabetes, is a heterogeneous and progressive disease with a variety of causative and potentiating factors. The hyperglycaemia of type 2 diabetes is ofte...

Increased formations of neutrophil extracellular traps are associated with gut leakage in the patients with type 1 diabetes but not type 2 diabetes.

The aims of this study were to investigate the association of formation of neutrophil extracellular traps (NETs) with gut leakage not only in type 1 diabetes (T1D) but also in type 2 diabetes (T2D).

Comorbidity Type and Health Care Costs in Type 2 Diabetes: A Retrospective Claims Database Analysis.

Previous studies suggest that the type and combination of comorbidities may impact diabetes care, but their cost implications are less clear. This study characterized how diabetes patients' health car...

Medical and Biotech [MESH] Definitions

The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).

A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.

A severe type of hyperlipidemia, sometimes familial, that it is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .

Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).

A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.

More From BioPortfolio on "Assessment of Beta Cell Mass in Type 1 Diabetes With 11C-Dihydrotetrabenazine and PET Scan"

Quick Search


Searches Linking to this Trial