Assessment of Insulin Production From Native Pancreas in Patients With Pancreas Transplants
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Long-Functioning Pancreas Allografts; Pancreas Transplant
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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.
Official title: Assessing Arginine-Stimulated Native Pancreas Insulin Production Via Selective Venous Sampling in Patients With Long-Functioning Pancreas Allografts
Study design: N/A
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.
Minimum age: 18 Years.
Maximum age: N/A.
- INCLUSION CRITERIA:
Patients will be included if:
Age greater than or equal to 18
GFR greater than 50 ml/min/1. 73 m2
History consistent with T1DM prior to pancreas transplant
Liver dysfunction (elevated liver enzymes, clinical evidence of portal hypertension)
coagulopathy (elevated INR or Partial Thromboplastin Time)
History of repeated instrumentation/cannulation in the jugular or femoral vessels
Known vascular anomalies
Anemia with Hgb less than 10
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Foulis AK, Liddle CN, Farquharson MA, Richmond JA, Weir RS. The histopathology of the pancreas in type 1 (insulin-dependent) diabetes mellitus: a 25-year review of deaths in patients under 20 years of age in the United Kingdom. Diabetologia. 1986 May;29(5):267-74.
Starting date: October 2005
Last updated: March 5, 2008