PET-CT Scan Method to Monitor Pancreatic B-Cell Loss in Diabetes Mellitus - Full Text View

Sponsors and Collaborators:	University of California, Irvine Juvenile Diabetes Research Foundation
Information provided by:	University of California, Irvine
ClinicalTrials.gov Identifier:	NCT00633763

Purpose

The pancreas is an organ that plays major roles in the digestion of food. A part of the pancreas called islet beta-cells produces insulin, which regulates the amount of glucose (a sugar) present in the blood at all times. Type-1 Diabetes Mellitus (T1DM), an autoimmune disorder characterized by destruction of pancreatic islet beta-cells (the cells that produce insulin), affects at least a million individuals in the US alone. In T1DM, a type of white blood cells called T lymphocytes attacks and destroys the pancreatic islet beta-cells, leading to a loss of insulin, an increase in blood glucose, and a dependence on insulin injections for survival. Despite rigorous control of blood sugar, the majority of diabetic patients develop serious complications including retinopathy, nephropathy, neuropathy, microangiopathy and strokes.

Non-invasive methods to monitor pancreatic beta-cell loss associated with type-1 diabetes mellitus (T1DM) could improve early diagnosis, provide tools to measure responsiveness to new therapies, and evaluate the efficiency of pancreatic transplantation and graft survival.

Our goal is to develop a non-invasive PET-CT imaging method based on binding of a molecule (18F-fallypride) for tracking beta-cell loss during the progression of T1DM. In preliminary studies we demonstrated specific binding of 18F-fallypride to D2 receptors in rat pancreatic sections and we demonstrated that the loss of pancreatic beta cells in streptozotocin-treated rats was associated with a corresponding decrease in 18F-fallypride binding to pancreatic sections. A preliminary 18F-fallypride PET-CT study done by a collaborator in Ohio on a healthy volunteer, revealed 18F-fallypride-uptake by the pancreas that was distinguishable from surrounding tissues. Aim-1 of our project will measure the variability of 18F-fallypride PET-scanning of the pancreas in six healthy volunteers scanned twice with an interval of 4-6 weeks. In Aim-2 of our project, we will compare fallypride PET-CT scans of 12 patients with long-standing T1DM (nearly all beta cells destroyed) with 12 age- and sex-matched healthy volunteers. If we are able to distinguish between the two groups, we will in future (a) optimize the method so as to be able to detect a 20-30% loss of beta cells, and (b) perform PET-CT studies in new-onset T1DM patients and in at-risk first degree relatives of T1DM patients.

Condition	Intervention
Type1 Diabetes Mellitus	Drug: 18F-fallypride

Study Type:	Observational
Study Design:	Case Control, Prospective
Official Title:	PET-CT Scan Method to Monitor Pancreatic B-Cell Loss in Diabetes Mellitus

Resource links provided by NLM:

MedlinePlus related topics: CT Scans Diabetes Diabetes Type 1 Nuclear Scans

Drug Information available for: Fallypride

U.S. FDA Resources

Further study details as provided by University of California, Irvine:

Primary Outcome Measures:

Difference in fallypride binding in the pancreas of long-standing T1DM patients versus healthy controls [ Time Frame: At the end of the study when 12 controls and 12 patients have been studied. ] [ Designated as safety issue: No ]

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment:	30
Study Start Date:	February 2008
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
1 Healthy individuals with normal C-peptide levels following i.v. glucagon challenge. These individuals will be administered 18F-fallypride and then subjected to PET-CT scanning of the pancreas and brain. The subject will be positioned in the PET/CT scanner and a low-dose CT (15-20 secs) of the abdomen carried out (with subjects breathing normally). A 30-min PET acquisition will then be started (three 10 min static frames or one 30 min static frame). The subject will then be repositioned for a low-dose CT scan of the head (15-20 secs) following which a 20-min PET acquisition will then be started (two 10 min static frames or one 20 min static frame).	Drug: 18F-fallypride Single bolus i.v. injection 60 minutes before PET-CT scanning. Maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms. Drug: 18F-fallypride I.v. bolus maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.
2 Patients with longstanding T1DM and <20% C-peptide levels following i.v. glucagon challenge will be consented. 18F-Fallypride injected intravenously and subjects allowed to wait for approx 1 hr for the uptake.(b) Subject positioned in the PET/CT scanner and a low-dose CT (15-20 secs) of the abdomen (pancreas) carried out (with subjects breathing normally).(c) A 30-min PET acquisition will then be started (three 10 min static frames or one 30 min static frame).(d) Subject repositioned for a low-dose CT scan of the head (15-20 secs).(e) A 20-min PET acquisition will then be started (two 10 min static frames or one 20 min static frame).(f) End of PET/CT scanning procedures. Subject taken out of the scanner.	Drug: 18F-fallypride Single bolus i.v. injection 60 minutes before PET-CT scanning. Maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms. Drug: 18F-fallypride I.v. bolus maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.

Groups/Cohorts

Assigned Interventions

1

Healthy individuals with normal C-peptide levels following i.v. glucagon challenge. These individuals will be administered 18F-fallypride and then subjected to PET-CT scanning of the pancreas and brain. The subject will be positioned in the PET/CT scanner and a low-dose CT (15-20 secs) of the abdomen carried out (with subjects breathing normally). A 30-min PET acquisition will then be started (three 10 min static frames or one 30 min static frame). The subject will then be repositioned for a low-dose CT scan of the head (15-20 secs) following which a 20-min PET acquisition will then be started (two 10 min static frames or one 20 min static frame).

Drug: 18F-fallypride

Single bolus i.v. injection 60 minutes before PET-CT scanning. Maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.

Drug: 18F-fallypride

I.v. bolus maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.

2

Patients with longstanding T1DM and <20% C-peptide levels following i.v. glucagon challenge will be consented. 18F-Fallypride injected intravenously and subjects allowed to wait for approx 1 hr for the uptake.(b) Subject positioned in the PET/CT scanner and a low-dose CT (15-20 secs) of the abdomen (pancreas) carried out (with subjects breathing normally).(c) A 30-min PET acquisition will then be started (three 10 min static frames or one 30 min static frame).(d) Subject repositioned for a low-dose CT scan of the head (15-20 secs).(e) A 20-min PET acquisition will then be started (two 10 min static frames or one 20 min static frame).(f) End of PET/CT scanning procedures. Subject taken out of the scanner.

Drug: 18F-fallypride

Single bolus i.v. injection 60 minutes before PET-CT scanning. Maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.

Drug: 18F-fallypride

I.v. bolus maximum activity per single administration 5 mCi; maximum amount of drug per administration <10 micrograms.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Joslin Diabetes Clinic at the University of California Irvine, age-matched controls will be obtained from Orange County California.

Criteria

Inclusion Criteria:

T1DM patients that are over 18 years of age, have had T1DM for greater than 5 years and show a greater than 80% reduction in C-peptide blood levels following intravenous glucagon injection are eligible to participate in this study.
Healthy controls that are over 18 years of age, show normal C-peptide blood levels following intravenous glucagon injection, and are age- and sex-matched with one of the T1DM patients included in the study, are eligible to participate in this study.

Exclusion Criteria:

T1DM patients or healthy controls that are not over 18 years of age are not eligible to participate in this study.
Pregnant females are not eligible to participate in this study because there is a chance PET/CT scans might be risky for the developing baby.

Females physically capable of getting pregnant will be required to get a urine pregnancy test at no cost before each of the PET/CT scans. If the pregnancy test is positive, the T1DM patient or healthy control will be excluded from the study. The consent form describes the risks in detail and the need for women of childbearing age to undergo a pregnancy test.

Subjects with a history of psychiatric illness, substance abuse history, clinically significant head trauma, active neurological disease, cardiovascular disease, liver disease or renal impairment, claustrophobia ((very upset and afraid of being in a small space) are not eligible for the study. Dr. Ping Wang will use the subjects history, blood chemistry, to identify individuals with cardiovascular disease, liver disease, or renal impairment.
T1DM patients with C-peptide levels following intravenous glucagon injection that are not reduced greater than 80% are not eligible for the study.
Healthy volunteers with C-peptide levels following intravenous glucagon injection that are reduced greater than 20% compared to established control values are not eligible for the study.
To determine if it is safe to do the procedure, T1DM patients and healthy volunteers will be expected to tell the researchers about any radiation exposure the individual may have had (including diagnostic or treatment x-rays), and any history of head injury, kidney or bladder disease, or any other serious medical conditions.
T1DM patients and healthy volunteers will be expected to tell the researchers if they have surgical clips or metallic prostheses (i.e., replacement body parts, such as a hip joint) or a pacemaker or other pieces of metal in the body (shrapnel, metal filings, etc.).
Patients with history of alcoholism or significant alcohol consumption will be excluded from the study.
The consent form will be English, and non-English speakers will therefore be excluded from the study.
Pregnant women are excluded because 18F-fallypride is a radioactive substance , which will be injected into the patient and could be hazardous to the fetus.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00633763

Locations

United States, California
University of California Irvine Medical Center
Orange, California, United States, 92868

Sponsors and Collaborators

University of California, Irvine

Juvenile Diabetes Research Foundation

Investigators

Principal Investigator:

George K Chandy, MD, PhD

University of California, Irvine

More Information

No publications provided

Responsible Party:	Department of Physiology and Biophysics, UC Irvine ( K. George Chandy, Professor )
Study ID Numbers:	2007-5785
Study First Received:	March 4, 2008
Last Updated:	May 27, 2009
ClinicalTrials.gov Identifier:	NCT00633763 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, Irvine:

Diagnostic
PET/CT imaging of pancreas
Detecting pancreatic beta cell loss during diabetes

Study placed in the following topic categories:

Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Diabetes Mellitus
Endocrine System Diseases

Diabetes Mellitus Type 1
Endocrinopathy
Glucose Metabolism Disorders
Pancrelipase
Metabolic Disorder

Additional relevant MeSH terms:

Autoimmune Diseases
Metabolic Diseases
Immune System Diseases
Diabetes Mellitus, Type 1

Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders

ClinicalTrials.gov processed this record on July 06, 2009