GLP-1 Effects on Insulin and Glucagon in PTDM

Post-transplant Diabetes Mellitus Clinical Trial

Official title:

GLP-1 Restores Altered Insulin and Glucagon Secretion in Post-transplantation Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02591849
• Other study ID #: 2014/666
• Status: Completed
• Phase: N/A
• First received: August 17, 2015
• Last updated: March 30, 2016
• Start date: October 2014
• Est. completion date: March 2015

Study information

• Verified date: March 2016
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: The Regional Comittees for Medical and Health Research Etichs in Norway
• Study type: Interventional

Clinical Trial Summary

Post-transplantation diabetes mellitus (PTDM) develops in 10-15 % of all renal transplant recipients within 10 weeks after transplantation, and has been associated with increased risk of cardiovascular disease and impaired patient survival. PTDM is primarily believed to be a variant of type 2 diabetes mellitus (T2DM), but the pathophysiology underlying the impaired glucose metabolism in renal transplant recipients with PTDM is unclear and some aspects are still poorly investigated. Hyperglycemic clamp investigations with concomitant infusion of glucagon-like peptide-1 (GLP-1) are warranted for a thorough characterization of the α-cell and β-cell function.

The primary objective of the present study is to investigate whether hyperglucagonemia is present in renal transplant recipients with PTDM. Furthermore, the investigators aim to examine the insulinotropic and glucagon suppressive effects of GLP-1 (compared to placebo) in PTDM patients during fasting glycemia and during hyperglycemic conditions (hyperglycemic clamp), respectively.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Renal transplant recipients more than 1 year post transplant with stable renal function (less than 20% deviation in serum creatinine within the last 2 months) and stable prednisolone dose (maximum 5 mg/day) the last three months before inclusion

• Diagnose of PTDM on standard clinical follow-up performed 8 weeks and 1 year post transplant at OUS-Rikshospitalet (fasting plasma glucose = 7.0 mmol/l and/or 2-hour plasma glucose = 11.1 mmol/l following an oral glucose tolerance test) OR

• Non-diabetic renal transplant recipients with a normal glucose tolerance test (control group)

• > 18 years of age

• BMI 18.5-29.9 kg/m2

• Signed informed consent

Exclusion Criteria:

• Severe liver disease

• Pancreatitis (chronic or acute), previous bowel resection, inflammatory bowel disease, malignancy (previous or actual)

• Estimated GFR < 25 ml/min/1.73 m2

• Pregnant or nursing mothers

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus
• Post-transplant Diabetes Mellitus

Intervention

Dietary Supplement:
• Glucagon-like peptide-1 (GLP-1)

Other:
• Isotonic saline

• Hyperglycemic clamp

Locations

Country	Name	City	State
Norway	Oslo University Hospital, Rikshospitalet	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Oslo University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of glucagon during fasting glycemia and during hyperglycemic conditions measured in picomoles per liter	The primary objective of the present study is to measure fasting plasma glucagon concentration and the suppression of glucagon during hyperglycemia (hyperglycemic clamp) measured in picomoles per liter with and without concomitant iv infusion of glucagon-like peptide-1 (GLP-1) in renal transplant recipients with and without PTDM	4 weeks	No
Secondary	Glucose-potentiated arginine test	Investigate the functional reserve capacity in glucagon and insulin release (measurement of functional a-cell and ß-cell mass) by a glucose-potentiated arginine test; since arginine is a glucose-independent stimulator of the release of both hormones.	4 weeks	No
Secondary	Insulin sensitivity index	Estimate insulin sensitivity index (ISI) by recording the glucose infusion rate during the hyperglycemic clamp, corrected for the prevailing plasma insulin concentrations.	4 weeks	No