Cardiovascular Risk Factors After Single Pancreas Transplantation

NCT02066350 | Completed

• 2 other identifiers: 2013/10622013047
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Type 1; Endothelial Dysfunction

Keywords

Diabetes type 1; Endothelial dysfunction; Pancreas transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Peripheral arterial tonometry

  1 year post-transplant

• Changes in cardiac performance

  1 year post-transplant

• Pulse wave velocity (arterial stiffness)

  1 year post-transplant

• Heart rate variability

  1 year post-transplant

• Plasma concentrations of endothelial dysfunction markers

  1 year post-transplant

Study Arms (1)

Single pancreas transplantation

EXPERIMENTAL

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. A control group of healthy volunteers (non-diabetic, non-transplanted), frequency-matched for age and gender with regards to the pancreas transplanted patients, will be investigated once.

Procedure: Single pancreas transplantation

Interventions

Single pancreas transplantation PROCEDURE

Single pancreas transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, N-0424, Norway

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Pancreas Transplantation

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Study Officials

• Trond G Jenssen, Professor

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor of Medicine

Study Record Dates

• First Submitted: February 14, 2014
• First Posted: February 19, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: February 1, 2017
• Last Updated: March 16, 2017

Record last verified: 2017-03

Locations

NO (1)