GLP-1 Effects on Insulin and Glucagon in PTDM

NCT ID: NCT02591849

Last Updated: 2016-03-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2015-03-31

Brief Summary

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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.

Detailed Description

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Conditions

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Post-transplant Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Blinding Strategy

NONE

Study Groups

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Glucagon-like peptide-1 (GLP-1)

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.

Group Type ACTIVE_COMPARATOR

Glucagon-like peptide-1 (GLP-1)

Intervention Type DIETARY_SUPPLEMENT

Hyperglycemic clamp

Intervention Type OTHER

Isotonic saline

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

Group Type PLACEBO_COMPARATOR

Isotonic saline

Intervention Type OTHER

Hyperglycemic clamp

Intervention Type OTHER

Interventions

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Glucagon-like peptide-1 (GLP-1)

Intervention Type DIETARY_SUPPLEMENT

Isotonic saline

Intervention Type OTHER

Hyperglycemic clamp

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Oslo University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Trond Jenssen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Oslo University Hospital, Rikshospitalet

Oslo, Oslo County, Norway

Site Status

Countries

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Norway

References

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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.

Reference Type DERIVED
PMID: 26908914 (View on PubMed)

Other Identifiers

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2014/666

Identifier Type: -

Identifier Source: org_study_id