Cirrhosis, Effects of TRAnsplantation and Diabetes (CETRA)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor:
Information provided by (Responsible Party):
Emanuela Orsi, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier:
NCT02038517
First received: January 10, 2014
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This observational study is aimed at assessing insulin secretion and sensitivity by the use of a mathematical modeling from oral glucose tolerance test in subjects with liver cirrhosis undergoing orthotopic liver transplantation (OLT), before and at various time points after OLT.


Condition
Liver Cirrhosis

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 10 Years
Official Title: Insulin Secretion and Sensitivity in Subjects With Liver Cirrhosis Undergoing Orthotopic Liver Transplantation (OLT): Pre- and Post-OLT Analysis

Resource links provided by NLM:


Further study details as provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:

Primary Outcome Measures:
  • Relationship of insulin secretion and sensitivity with the development of abnormalities of glucose metabolism after OLT [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Relation between baseline values and changes with transplantation of measures of insulin secretion and sensitivity, as derived from of the analysis of OGTT by the use of a mathematical model (i.e. proportional and derivative control for insulin secretion and oral glucose insulin sensitivity - OGIS - for insulin sensitivity ) and the development of abnormalities of glucose metabolism after OLT.


Secondary Outcome Measures:
  • Relationship of insulin secretion and sensitivity with morbidity and mortality after OLT [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Relation between baseline values and changes with transplantation of measures of insulin secretion and sensitivity, as derived from of the analysis of OGTT by the use of a mathematical model (i.e. proportional and derivative control for insulin secretion and oral glucose insulin sensitivity - OGIS - for insulin sensitivity ) and morbidity and mortality after OLT.

  • Relationship of insulin secretion and sensitivity with the development of the metabolic syndrome after OLT [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Relation between baseline values and changes with transplantation of measures of insulin secretion and sensitivity, as derived from of the analysis of OGTT by the use of a mathematical model (i.e. proportional and derivative control for insulin secretion and oral glucose insulin sensitivity - OGIS - for insulin sensitivity ) and the development of the metabolic syndrome and its components (impaired glucose metabolism, central obesity, dyslipidemia and hypertension) after OLT.


Other Outcome Measures:
  • Prevalence and incidence of impaired glucose metabolism (IFG, IGT and diabetes) [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Prevalence of unknown diabetes mellitus or IGT (normal levels of fasting glucose and HbA1c) pre-OLT and incidence of new-onset diabetes after transplantation (NODAT) or IFG/IGT

  • Prevalence and incidence of the metabolic syndrome and its components (central) obesity , dyslipidemia and hypertension [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Prevalence of the metabolic syndrome and its components (National Cholesterol Education Program - Adult Treatment Panel criteria, 2004 revision) pre-OLT and incidence of new-onset metabolic syndrome after transplantation

  • Morbidity and mortality after OLT [ Time Frame: 10 years ] [ Designated as safety issue: No ]
    Morbidity and mortality from OLT-related and unrelated causes, including rejection, infection, and cardiovascular disease


Biospecimen Retention:   Samples With DNA

Serum, plasma, urines and DNA


Estimated Enrollment: 200
Study Start Date: June 2013
Estimated Study Completion Date: December 2024
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Background

Diabetes is frequent in subjects with liver cirrhosis, especially in those with liver disease related to alcohol, hepatitis C, hemochromatosis and NASH, though it goes often unrecognised if screened by measuring fasting glucose. These individuals might suffer from classical type 2 diabetes, in which β-cell dysfunction plays a major role, or from hepatogenous diabetes, in which insulin resistance predominates. Orthotopic liver transplantation (OLT) improves life quality and expectancy of individuals with end-stage liver cirrhosis, thus representing the elective treatment for these patients. OLT has different effects on glucose metabolism. On the one hand, restoration of liver function reduces insulin resistance by improving hepatic insulin clearance, thus favouring regression of hepatogenous diabetes. On the other hand, OLT may worsen insulin secretion and sensitivity, due to immunosuppression and lifestyle modifications, with return to free food intake.

Aims

This observational study is aimed at assessing insulin secretion and sensitivity by the use of a mathematical modeling from oral glucose tolerance test in subjects with liver cirrhosis undergoing orthotopic liver transplantation (OLT), before and at various time points after OLT over a 10-year follow-up and to establish the relation of alterations in insulin secretion and sensitivity and their changes with transplantation with the development or persistence of abnormalities of glucose metabolism after OLT.

Secondary endpoints are to assess in these individuals:

  • the relation of alterations in insulin secretion and sensitivity and their changes with transplantation with morbidity and mortality after OLT;
  • the relation of alterations in insulin secretion and sensitivity and their changes with transplantation with the development or persistence of the metabolic syndrome and its components (central) obesity , dyslipidemia and hypertension;

Other pre-specified endpoints are to assess in these subjects:

  • prevalence and incidence of unknown diabetes mellitus (and IFG/IGT);
  • prevalence and incidence of the metabolic syndrome and its components (central) obesity , dyslipidemia and hypertension;
  • morbidity and mortality from OLT-related and unrelated causes, including rejection, infection, and cardiovascular disease.

Patients Consecutive patients with normal fasting plasma glucose and HbA1c levels in waiting list for OLT will be recruited from electronic records of the diabetic clinic of the Endocrinology and Diabetes Unit, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy.

Measures

Routine clinical and laboratory data will be recorded at baseline and over the subsequent 10 years to obtain information about:

  • cardiovascular risk factors (smoking, physical activity, family history of diabetes, dyslipidemia, hypertension and cardiovascular disease, BMI and waist circumference, total, LDL, HDL and non-HDL cholesterol, triglycerides, arterial blood pressure and HbA1c);
  • cardiovascular events (myocardial infarction, stroke, lower limb ulcer/gangrene/amputation and coronary, carotid and lower limb revascularization, endovascular/surgical) and deaths.
  • renal function (albumin/creatinine ratio, serum creatinine with estimation of glomerular filtration rate [eGFR]);
  • current glucose-, lipid- and blood pressure-lowering and anti-platelet or anti-coagulant treatment;
  • other illnesses and non-cardiovascular deaths. In addition, glucose, insulin and C-peptide levels from blood sample collected before and 15, 30, 45, 60, 90, 120', 150, and 180 min after a 75 g oral glucose tolerance test (OGTT) will be recorded. This test is routinely performed to all cirrhotic subjects before and at various time points after OLT. The response to OGTT will be evaluated by the use of a mathematical model to derive measures of insulin secretion (Proportional and Derivative Control) and sensitivity (OGIS, Oral Glucose Insulin Sensitivity).

Time schedule

This observational study was submitted for approval to the Ethics Committee of the Organization (Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy) on October 24, 2012. The transferral of patient records (concerning the 2007-2013 visits) from the electronic database of the centre to the study database has been started on June 2013 and will terminate on September 2014.

The enrolled patients will be followed for at least 10 years with (at least) yearly visits and consultation of death records in case of drop-out for unknown reasons.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Secondary care outpatients clinic

Criteria

Inclusion Criteria:

Subjects with end-stage liver cirrhosis in waiting list for orthotopic liver transplantation at the Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy

Exclusion Criteria:

  • Known diabetes
  • Cystic fibrosis
  • Pregnancy
  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: NCT02038517

Contacts
Contact: Emanuela Orsi, MD +390255034590 e.orsi@policlinico.mi.it

Locations
Italy
Endocrinology and Diabetes Unit, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico Recruiting
Milan, MI, Italy, 20122
Contact: Emanuela Orsi, MD    +390255034590    e.orsi@policlinico.mi.it   
Sub-Investigator: Elena Lunati, MD         
Sub-Investigator: Valeria Grancini, MD         
Sub-Investigator: Eva Palmieri, MD         
Sub-Investigator: Dario Zimbalatti, MD         
Sub-Investigator: Veronica Resi, MD         
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Investigators
Principal Investigator: Emanuela Orsi, MD Endocrinology and Diabetes Unit, Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy
  More Information

No publications provided

Responsible Party: Emanuela Orsi, MD, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT02038517     History of Changes
Other Study ID Numbers: EDOMP-1301
Study First Received: January 10, 2014
Last Updated: March 24, 2014
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Insulin secretion
Insulin sensitivity
Orthotopic liver transplantation
Type 2 diabetes
Metabolic syndrome
Cardiovascular disease

Additional relevant MeSH terms:
Liver Cirrhosis
Fibrosis
Liver Diseases
Digestive System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 26, 2014