Clinical trial NCT02066350: Cardiovascular Risk Factors After Single Pancreas Transplantation
Official title: Assessment of Cardiovascular Risk Factors, Including Endothelial Function, After Restoration of Normoglycemia Following Single Pancreas Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Type 1
Endothelial Dysfunction
Keywords: Diabetes type 1
Endothelial dysfunction
Pancreas transplantation
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
First posted: 2014-02-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Patients accepted for the waiting list for single pancreas transplantation suffer from severe glucose instability with hyperglycemia due to diabetes type 1, but do not have significant diabetes-related complications. Pancreas transplantation restores normoglycemia in diabetes type 1 patients with unstable control of glycemia. Both hypo- and hyperglycemic events are abolished, and 70-80 % of the patients obtain satisfactory HbA1c levels (HbA1c 5.0-6.0 %) without the need of exogenous insulin. Endothelial dysfunction is considered as an early and potentially reversible stage in the atherosclerotic process. The endothelium is involved in homeostasis, leucocyte adhesion and vasomotor activity. Reduced endothelium-dependent vasodilation is associated with increments in cardiovascular risk factors, and endothelial dysfunction is a predictor for future cardiovascular disease. It has also been hypothesized that endothelial dysfunction may be involved in the impaired glycemic control by reducing the availability of glucose in peripheral muscles.Establishing normoglycemia by pancreas transplantation alone in previously diabetic type 1 patients has recently been shown to improve left ventricular ejection fraction, assessed by Doppler echocardiographic examination. In diabetic patients receiving a new pancreas it is possible to assess the effect of changing blood glucose excursions on cardiovascular risk factors, including endothelial function, without the use of antidiabetic drugs (exclude pleiotropic effects).

The primary objective of the present study is to assess if endothelial function (assessed by flow-mediated dilatation of arteria brachialis) is improved when hyperglycemia is reversed by single pancreas transplantation in patients with type 1 diabetes.

Secondary objectives are to investigate the changes in the following parameters by reversal of hyperglycemia by pancreas transplantation; Peripheral arterial tonometry, serum/plasma concentrations of endothelial dysfunction markers, blood pressure, lipid and lipoprotein concentrations.


Eligibility criteria: Inclusion Criteria:

* Patients with type 1 diabetes accepted for the waiting list for single pancreas transplantation
* Healthy volunteers (non-diabetic, non-transplanted)
* Over 18 years of age
* Signed informed consent

Exclusion Criteria:

* Non-functioning pancreas graft (defined as HbA1c ≥ 6.5 % with the need of insulin injections and fasting C-peptide concentration \< 300 pmol/L).
* Active infection
* Active autoimmune disease other than diabetes
* Severe liver disease

Primary outcomes:
measure: Endothelial function
timeFrame: 1 year post-transplant
Secondary outcomes:
measure: Peripheral arterial tonometry
timeFrame: 1 year post-transplant
measure: Changes in cardiac performance
timeFrame: 1 year post-transplant
measure: Pulse wave velocity (arterial stiffness)
timeFrame: 1 year post-transplant
measure: Heart rate variability
timeFrame: 1 year post-transplant
measure: Plasma concentrations of endothelial dysfunction markers
timeFrame: 1 year post-transplant
measure: Blood pressure
timeFrame: 1 year post-transplant
measure: Lipid and lipoprotein concentrations
timeFrame: 1 year post-transplant
measure: Bone mineral density and body composition
timeFrame: 1 year post-transplant
measure: Glomerular filtration rate
timeFrame: 1 year post-transplant
measure: Oral glucose tolerance test
timeFrame: 1 year post-transplant
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital, Rikshospitalet
Study officials:
affiliation: Oslo University Hospital
name: Trond G Jenssen, Professor
role: PRINCIPAL_INVESTIGATOR
References: