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Completed

NCT Number: NCT02066350

Cardiovascular Risk Factors After Single Pancreas Transplantation

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.

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Key information

Conditions

Diabetes Type 1 Autoimmune Diseases Diabetes Mellitus Diabetes Mellitus, Type 1 Endocrine System Diseases Endothelial Dysfunction Glucose Metabolism Disorders Immune System Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Oslo University Hospital, Rikshospitalet

Oslo, N-0424, Norway

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Single pancreas transplantation

Procedure

Primary outcomes

  1. Endothelial function

    Time frame: 1 year post-transplant

    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.

Secondary outcomes

  1. Peripheral arterial tonometry

    Time frame: 1 year post-transplant

  2. Changes in cardiac performance

    Time frame: 1 year post-transplant

    An echocardiographic examination will be performed to assess changes in cardiac performance, such as left ventricular ejection fraction

  3. Pulse wave velocity (arterial stiffness)

    Time frame: 1 year post-transplant

    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.

  4. Heart rate variability

    Time frame: 1 year post-transplant

    Heart rate variability will be assessed, using a Vagus device, analyzing short-term electrocardiogram recordings.

  5. Plasma concentrations of endothelial dysfunction markers

    Time frame: 1 year post-transplant

    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).

  6. Blood pressure

    Time frame: 1 year post-transplant

    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.

  7. Lipid and lipoprotein concentrations

    Time frame: 1 year post-transplant

  8. Bone mineral density and body composition

    Time frame: 1 year post-transplant

    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.

  9. Glomerular filtration rate

    Time frame: 1 year post-transplant

    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.

  10. Oral glucose tolerance test

    Time frame: 1 year post-transplant

    Measurements of plasma glucose, C-peptide and serum insulin before, 30 and 120 minutes following an oral administration of 75 g glucose.

Sponsors and collaborators

Lead sponsor

Oslo University Hospital

Other

Registry information

Official study title

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

Acronym: Diamant

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Feb 19, 2014
Registry last updated
Mar 16, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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