Assessment of Insulin Production From Native Pancreas in Patients With Pancreas Transplants
Summary
This study will examine whether insulin-producing cells in the pancreas (beta cells) can recover in patients with type 1 diabetes who have had a pancreas transplant. In type 1 diabetes, the body's immune system destroys the beta cells. Patients are treated with insulin shots or a pancreas transplant to control their blood sugar. Some experiments suggest that the pancreas may have the capacity to recover some of its insulin-producing capacity, but that ability is negated by factors such as the continuing immune attack and erratic blood sugar levels in patients.
Patients who have had a pancreas transplant may be in a unique situation to allow their own pancreas to regrow beta cells for two reasons: 1) the medicines they take to prevent rejection of the transplanted pancreas weaken their immune system; and 2) they have near-normal blood sugar levels because of their functioning transplanted pancreas. This study will test this hypothesis by sampling blood from patients' hepatic vein, which drains the liver and native pancreas and from their iliac vein, which drains the transplanted pancreas. This will determine whether insulin is coming from the transplanted pancreas (iliac vein) or the liver and native pancreas (hepatic vein).
Patients 18 years of age and older who have had stable pancreatic transplant function for more than 5 years may be eligible for this study. Candidates are screened with a medical history and physical examination.
Participants are admitted to the hospital for 2 days for a full medical examination, blood tests and procedures to determine insulin production. The procedures will include the placement of catheters in the neck and groin for blood sampling. Participants will be closely monitored after the procedures and discharged home if there are no complications.
Description
Type 1 diabetes mellitus (T1DM) is thought to result from an autoimmune destruction of insulin producing beta-cells found within the pancreatic islets of Langerhans. In addition to the autoimmune process however, many studies have shown that hyperglycemia is also toxic to islets. Interventional studies have shown, for instance, that either tight glycemia control or immunosuppression can preserve C-peptide production. We hypothesize that patients who are immunosuppressed and euglycemic will display evidence that their native pancreas has recovered beta-cell function. We have asked whether pancreas transplant recipients, due to the immunosuppression required to prevent allograft loss, and the improved glycemia control resulting from the transplanted pancreas, might display some recovery of their native pancreatic islet function. Our preliminary data suggest that patients without C-peptide production prior to receiving an islet transplant appear to recover some endogenous pancreatic insulin secretion after islet transplantation. We will study whole pancreas transplant recipients, specifically those with grafts functioning for at least 5 years. We will test for native pancreas insulin production by infusing arginine into a peripheral vein, then selectively/simultaneously sampling blood for C-peptide levels from the hepatic veins and the vein draining the pancreatic allograft . Unlike our previous study of islet transplant recipients, a study that required portal vein cannulation, this study will require only hepatic and iliac vein cannulations, both much easier to accomplish, and associated with much less risk to the patient. Samples obtained from these sites will be tested for C-peptide levels. In addition, if we find evidence of native pancreas insulin production, we will look at a variety of clinical variables to see if any correlate with recovery of function.
Study Design
N/A
Conditions
Long-Functioning Pancreas Allografts
Location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892
Status
Completed
Source
National Institutes of Health Clinical Center (CC)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00246844
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Pancreas Transplantation
The transference of a pancreas from one human or animal to another.
Pancreas, Exocrine
The major component (about 80%) of the PANCREAS composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as TRYPSINOGEN; LIPASE; AMYLASE; and RIBONUCLEASE. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the DUODENUM.
Colipases
Colipase I and II, consisting of 94-95 and 84-85 amino acid residues, respectively, have been isolated from porcine pancreas. Their role is to prevent the inhibitory effect of bile salts on the lipase-catalyzed intraduodenal hydrolysis of dietary long-chain triglycerides.
Histocompatibility
The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts.
Pancreatic Pseudocyst
Cyst-like space not lined by EPITHELIUM and contained within the PANCREAS. Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic PANCREATITIS.
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