GLP-1 Effects on Insulin and Glucagon in PTDM

NCT02591849 | Completed

• 1 other identifier: 2014/666
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post-transplant Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Glucose-potentiated arginine test

  4 weeks

• Insulin sensitivity index

  4 weeks

Study Arms (2)

Glucagon-like peptide-1 (GLP-1)

ACTIVE COMPARATOR

Twelve eligible renal transplant recipients with PTDM and twelve age, gender, BMI and renal function-matched non-diabetic renal transplant recipients will be randomized to continuous unblinded intravenous infusion of GLP-1 with an infusion rate of 0.8 pmol/kg/min or isotonic saline (placebo) on two experimental days performed 2-4 weeks apart. The GLP-1 infusion will consist of 42.5 nmol/mL GLP-1 (7-36) amide, 12.5 mL 5% human albumin and isotonic saline added to a total volume of 50 mL. After 60 min, a 2 hour hyperglycemic clamp will be initiated, where plasma glucose will be elevated by 5 mmol/L from each individual fasting plasma glucose in both groups. This will be done to measure concentrations of glucagon and insulin in hyperglycemic conditions.

Dietary Supplement: Glucagon-like peptide-1 (GLP-1); Other: Hyperglycemic clamp

Isotonic saline

PLACEBO COMPARATOR

The included patients will receive concomitant intravenous infusion of isotonic saline on one of the two experimental days

Other: Isotonic saline; Other: Hyperglycemic clamp

Interventions

Glucagon-like peptide-1 (GLP-1) DIETARY_SUPPLEMENT

Glucagon-like peptide-1 (GLP-1)

Isotonic saline OTHER

Isotonic saline

Hyperglycemic clamp OTHER

Glucagon-like peptide-1 (GLP-1); Isotonic saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, N-0424, Norway

Location

Related Publications (1)

• Halden TA, Egeland EJ, Asberg A, Hartmann A, Midtvedt K, Khiabani HZ, Holst JJ, Knop FK, Hornum M, Feldt-Rasmussen B, Jenssen T. GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes. Diabetes Care. 2016 Apr;39(4):617-24. doi: 10.2337/dc15-2383. Epub 2016 Feb 23.

  PMID: 26908914 DERIVED

MeSH Terms

Interventions

Glucagon-Like Peptide 1; Sodium Chloride

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 17, 2015
• First Posted: October 30, 2015
• Study Start: October 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 31, 2016

Record last verified: 2016-03

Locations

NO (1)