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Cardiovascular Risk Factors After Single Pancreas Transplantation (Diamant)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Oslo University Hospital
Sponsor:
Information provided by (Responsible Party):
Trond Jenssen, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT02066350
First received: February 14, 2014
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention
Diabetes Type 1
Endothelial Dysfunction
Procedure: Single pancreas transplantation

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Assessment of Cardiovascular Risk Factors, Including Endothelial Function, After Restoration of Normoglycemia Following Single Pancreas Transplantation

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Endothelial function [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Peripheral arterial tonometry [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Changes in cardiac performance [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    An echocardiographic examination will be performed to assess changes in cardiac performance, such as left ventricular ejection fraction

  • Pulse wave velocity (arterial stiffness) [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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.

  • Heart rate variability [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    Heart rate variability will be assessed, using a Vagus device, analyzing short-term electrocardiogram recordings.

  • Plasma concentrations of endothelial dysfunction markers [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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).

  • Blood pressure [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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.

  • Lipid and lipoprotein concentrations [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
  • Bone mineral density and body composition [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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.

  • Glomerular filtration rate [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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.

  • Oral glucose tolerance test [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    Measurements of plasma glucose, C-peptide and serum insulin before, 30 and 120 minutes following an oral administration of 75 g glucose.


Estimated Enrollment: 30
Study Start Date: January 2014
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single pancreas transplantation
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02066350

Contacts
Contact: Trond G Jenssen, Professor +47 23071907 tjenssen@ous-hf.no
Contact: Thea AS Halden, PhD-student +47 23073544 strthe@ous-hf.no

Locations
Norway
Oslo University Hospital, Rikshospitalet Recruiting
Oslo, Norway, N-0424
Contact: Trond G Jenssen, Professor    +47 23071907    tjenssen@ous-hf.no   
Principal Investigator: Trond G Jenssen, Professor         
Sub-Investigator: Thea AS Halden, PhD-student         
Sub-Investigator: Anders Hartmann, Professor         
Sub-Investigator: Anders Åsberg, Professor         
Sponsors and Collaborators
Oslo University Hospital
Investigators
Principal Investigator: Trond G Jenssen, Professor Oslo University Hospital
  More Information

No publications provided

Responsible Party: Trond Jenssen, MD, PhD, Professor of Medicine, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT02066350     History of Changes
Other Study ID Numbers: 2013/1062, 2013047
Study First Received: February 14, 2014
Last Updated: February 17, 2014
Health Authority: Norway: Regional Ethics Commitee

Keywords provided by Oslo University Hospital:
Diabetes type 1
Endothelial dysfunction
Pancreas transplantation

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Autoimmune Diseases
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Pancreatin
Pancrelipase
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014