Cardiovascular Risk Factors After Single Pancreas Transplantation

Endothelial Dysfunction Clinical Trial

— Diamant  

Official title:

Assessment of Cardiovascular Risk Factors, Including Endothelial Function, After Restoration of Normoglycemia Following Single Pancreas Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02066350
• Other study ID #: 2013/1062
• Secondary ID: 2013047
• Status: Completed
• Phase: N/A
• First received: February 14, 2014
• Last updated: March 15, 2017
• Start date: January 2014
• Est. completion date: February 2017

Study information

• Verified date: March 2017
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Diabetes Type 1
• Endothelial Dysfunction

Intervention

Procedure:
• Single pancreas transplantation

Locations

Country	Name	City	State
Norway	Oslo University Hospital, Rikshospitalet	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function	This is an explorative analysis to assess the impact of establishing normoglycemia in previously hyperglycemic patients, without using antidiabetic drugs, by investigating patients before and after single pancreas transplantation. Active patients on the waiting list for single pancreas transplantation will be investigated while on the waiting list and subsequently 8 weeks and 1 year after transplantation if they have a functioning pancreas graft. Flow-mediated dilatation (FMD) of large vessels (arteria brachialis) will be assessed by measuring vessel diameter by ultrasound and the FMD of micro vessels in the finger tip will be assessed by Endo-PAT (PAT=Peripheral Arterial Tonus) following reactive hyperperfusion induced by occlusion of the artery by a sphygmomanometer cuff.	1 year post-transplant
Secondary	Peripheral arterial tonometry		1 year post-transplant
Secondary	Changes in cardiac performance	An echocardiographic examination will be performed to assess changes in cardiac performance, such as left ventricular ejection fraction	1 year post-transplant
Secondary	Pulse wave velocity (arterial stiffness)	Pulse wave velocity, using a SphygmoCor device, measuring arterial stiffness will be performed in addition to pulse wave analysis evaluating the shape and amplitude of the aortic pulse wave.	1 year post-transplant
Secondary	Heart rate variability	Heart rate variability will be assessed, using a Vagus device, analyzing short-term electrocardiogram recordings.	1 year post-transplant
Secondary	Plasma concentrations of endothelial dysfunction markers	Fasting plasma samples (6 mL EDTA vacutainer) will be drawn for determination of relevant markers for endothelial dysfunction, such as von Willebrand factors (vWF) and vascular cell adhesion molecule-1 (VCAM-1).	1 year post-transplant
Secondary	Blood pressure	Blood pressure will be measured seated after ten minutes rest by Dyna Map (Tuff.-Cuff, CAS Medical system Inc.) and the mean of the lower two out of three measurements will be used.	1 year post-transplant
Secondary	Lipid and lipoprotein concentrations		1 year post-transplant
Secondary	Bone mineral density and body composition	Measurement of bone mineral density, using low dosage radiation (dual-energy X-ray absorptiometry (DEXA) scan) to assess the amount (grams) of mineral that are packed into a segment of bone. In addition a body composition (visceral fat, metabolic measurement) will be determined using the DEXA scan.	1 year post-transplant
Secondary	Glomerular filtration rate	Renal function, defined as glomerular filtration rate, will be evaluated by measuring iohexol clearance. The concentration of iohexol (Omnipaque), a low dose non-ionic x-ray contrast medium of low osmolality, extensively used in clinical radiology and considered essentially free from side effects, will be measured 2 hours and 5 hours after iv injection of iohexol. Like other iodine-containing contrast media, it is completely eliminated from the body by excretion in the urine, thus it is an ideal marker for kidney function. It will be quantitated by chemical measurement based on the determination of iodine.	1 year post-transplant
Secondary	Oral glucose tolerance test	Measurements of plasma glucose, C-peptide and serum insulin before, 30 and 120 minutes following an oral administration of 75 g glucose.	1 year post-transplant