Intact Liver Innervation and Glucose and Glucagon-like Peptide-1 (GLP-1) Induced Insulin Secretion

Liver Transplantation Clinical Trial

Official title:

The Significance of Intact Liver Innervation for the Glucose and GLP-1 Induced Insulin Secretion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01176708
• Other study ID #: Transplant isoglycemia (AP)
• Status: Recruiting
• Phase: N/A
• First received: August 5, 2010
• Last updated: January 5, 2012
• Start date: July 2009
• Est. completion date: December 2012

Study information

• Verified date: January 2012
• Source: University Hospital, Gentofte, Copenhagen
• Contact: Astrid Plamboeck, M.D.
• Phone: +45 26208174
• Email: astridp[@]sund.ku.dk
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to investigate the significance of intact nerve supply to the liver for the glucagon-like peptide-1 (GLP-1) induced insulin secretion.

The hypothesis is that the effects of GLP-1 is transmitted through the GLP-1 receptor and that these effects involve sensory afferent neurons, probably primarily parasympathetic.

Description:

GLP-1 is a potent enterogastron and incretin hormone. It is rapidly inactivated by dipeptidyl peptidase IV so only 10-15% enters the systemic circulation. This has led to the hypothesis that GLP-1 interact locally with afferent sensory nerve fibers.

The aim of this study is to investigate the significance of intact liver innervation for the GLP-1 induced insulin secretion in liver transplanted patients; kidney transplanted control patients matched for immunosuppressive treatment, age, gender and body weight; and ten control persons matched for age, gender and body weight.

The insulin secretion will be evaluated from blood samples that will be analyzed for insulin and c-peptide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• normal fasting plasma glucose

• normal hemoglobin

• informed consent

Exclusion Criteria:

• type 1 diabetes mellitus or type 2 diabetes mellitus

• body mass index > 30

• inflammatory bowel disease

• intestinal surgery

• serum creatinine > 250 µM and/or albuminuria

• ALAT > 2 x normal value

• Severe cardiac insufficiency

• in treatment with medicine which cannot be paused for 12 hours

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• dipeptidyl peptidase 4 (DPP4) inhibitor
One tablet (50 mg)of DPP4 inhibitor is to be taken 12 and 1 hours before start of the oral glucose tolerance test (50 g glucose and 1.5 g paracetamol dissolved in 300 ml water)on day 3

Other:
• oral glucose
50 grams glucose dissolved in 300 ml water with 1.5 grams paracetamol
• intravenous glucose
1.5 g paracetamol dissolved in 50 ml water is to be ingested orally within the first 2 minutes. Intravenous glucose is supplied in an amount to match the plasma glucose during the oral glucose tolerance test

Locations

Country	Name	City	State
Denmark	Department of Internal Medicine F' laboratory	Hellerup	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	insulin secretion	The insulin secretion during a four-hour oral glucose tolerance test (OGTT) and an intravenous isoglycaemic clamp is evaluated	four hours	No
Secondary	plasma glucose	20 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour	20 time points within four hours	No
Secondary	plasma GLP-1	12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour	12 time points within four hours	No
Secondary	plasma GIP	12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour	12 time points within four hours	No
Secondary	plasma glucagon	12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour	12 time points within four hours	No
Secondary	plasma GLP-2	12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour.	12 time points within four hours	No
Secondary	plasma PYY	12 blood samples will be drawn during the four hours OGTT and intravenous isoglycaemic clamp, most frequently during the first hour	12 time points within four hours	No