Cardiovascular Risk Factors After Single Pancreas Transplantation (Diamant)
Assessment of Cardiovascular Risk Factors, Including Endothelial Function, After Restoration of Normoglycemia Following 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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Tipo di studio
Iscrizione (Effettivo)
Fase
- Non applicabile
Contatti e Sedi
Luoghi di studio
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Oslo, Norvegia, N-0424
- Oslo University Hospital, Rikshospitalet
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Scienza basilare
- Assegnazione: N / A
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Endothelial function
Lasso di tempo: 1 year post-transplant
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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.
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1 year post-transplant
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Peripheral arterial tonometry
Lasso di tempo: 1 year post-transplant
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1 year post-transplant
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Changes in cardiac performance
Lasso di tempo: 1 year post-transplant
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An echocardiographic examination will be performed to assess changes in cardiac performance, such as left ventricular ejection fraction
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1 year post-transplant
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Pulse wave velocity (arterial stiffness)
Lasso di tempo: 1 year post-transplant
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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.
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1 year post-transplant
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Heart rate variability
Lasso di tempo: 1 year post-transplant
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Heart rate variability will be assessed, using a Vagus device, analyzing short-term electrocardiogram recordings.
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1 year post-transplant
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Plasma concentrations of endothelial dysfunction markers
Lasso di tempo: 1 year post-transplant
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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).
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1 year post-transplant
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Blood pressure
Lasso di tempo: 1 year post-transplant
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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.
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1 year post-transplant
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Lipid and lipoprotein concentrations
Lasso di tempo: 1 year post-transplant
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1 year post-transplant
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Bone mineral density and body composition
Lasso di tempo: 1 year post-transplant
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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.
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1 year post-transplant
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Glomerular filtration rate
Lasso di tempo: 1 year post-transplant
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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.
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1 year post-transplant
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Oral glucose tolerance test
Lasso di tempo: 1 year post-transplant
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Measurements of plasma glucose, C-peptide and serum insulin before, 30 and 120 minutes following an oral administration of 75 g glucose.
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1 year post-transplant
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Collaboratori e investigatori
Sponsor
Investigatori
- Investigatore principale: Trond G Jenssen, Professor, Oslo University Hospital
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 2013/1062
- 2013047 (Altro numero di sovvenzione/finanziamento: South-Eastern Norway Regional Health Authority)
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