- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01391884
Elimination of Incretin Hormones in Patients With Severe Kidney Failure
Elimination and Biodegradation of the Incretin Hormones GLP-1 and GIP in Patients With End-stage Renal Disease
The prevalence of type 2 diabetes (T2D) is increasing rapidly worldwide. T2D is characterized by a severely impaired incretin effect. The incretin effect refers to the insulinotropic action of the nutrient-released incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The incretin effect is defined as the difference in insulin secretory responses between oral and isoglycaemic intravenous glucose challenges (OGTT and IIGI, respectively) and in healthy individuals it accounts for as much as 70% of the insulin response following oral glucose, whereas patients with T2D exhibit an incretin effect in the range of 0 to 30%. Patients with T2D and non-diabetic patients with severe kidney failure share several pathophysiological characteristics, including decreased insulin sensitivity, fasting hyperinsulinaemia and impaired beta-cell function. The reason for these findings remains to be fully elucidated. An ongoing study in our research group is investigating the incretin effect and the incretin hormone secretory responses following OGTT, IIGI and meal ingestion, respectively. In continuation of this study, essential knowledge of metabolism of incretin hormones in an uremic milieu will be obtained in the present study prior to evaluation of the use of incretin-based agents in patients with impaired kidney function. In this second study we evaluate the elimination and biodegradation of GLP-1 and GIP. The biological active incretin hormones are rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4), generating inactive metabolites. The active hormones are however also eliminated by renal clearance, although the importance of this remains questionable. It is likely that the degradation and elimination of the active hormones will be significantly affected in patients with severe kidney impairment.
We hypothesize that elimination and biodegradation of the two incretin hormones, both in it´s active and inactive forms, will be affected in non-diabetic patients with severe kidney failure.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Copenhagen, Denmark, 2100
- Department of Nephrology P, Copenhagen University Hospital, Rigshospitalet
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
- Hemodialysis patients
- Healthy control subjects
Description
1)
Inclusion Criteria:
- Male or female; aged 18-90 years
- CKD stage 5 in chronic maintenance dialysis treatment
- BMI: 18,5-28 kg/m2
- Normal fasting plasma glucose (<6,1 mM)
- Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)
Inclusion Criteria:
- Male or female; aged 18-90 years
- Healthy including normal kidney function
- BMI: 18,5-28 kg/m2
- Normal fasting plasma glucose (<6,1 mM)
- Normal or impaired glucose tolerance (PG120 min <11,1 mM following OGTT)
1+2)
Exclusion Criteria:
- Diabetes mellitus
- Chronic pancreatitis / previous acute pancreatitis
- Treatment with oral glucocorticoids, calcineurin inhibitors, thiazides, dipeptidyl peptidase 4 (DPP4) inhibitors or other drugs, which could interfere with glucose or lipid metabolism
- Inflammatory bowel disease
- Malignant disease
- Bowel resection
- Severe anemia (hemoglobin <6.5 mmol/L)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
---|
Healthy control
|
Dialysis, Non-diabetic
Hemodialysis
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Intact GLP-1 concentration
Time Frame: -60 min - 180 min
|
During GLP-1 infusion 0-60 min
|
-60 min - 180 min
|
Total GLP-1 concentration
Time Frame: -60 min - 180 min
|
GLP-1 infusion 0-60 min
|
-60 min - 180 min
|
Intact GIP concentration
Time Frame: - 60 min - 180 min
|
GIP infusion 0-60 min
|
- 60 min - 180 min
|
Total GIP infusion
Time Frame: -60 min - 180 min
|
GIP infusion 0-60 min
|
-60 min - 180 min
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-2-2009-158-UREMINC
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Uremia
-
Herlev HospitalFlexdialysis ApSCompleted
-
Fuzhou General HospitalTerasaki FoundationUnknownRenal Transplantation | UremiaChina
-
Miulli General HospitalUnknown
-
Suzhou Municipal HospitalThe First Affiliated Hospital with Nanjing Medical University; The First Affiliated... and other collaboratorsNot yet recruiting
-
Rigshospitalet, DenmarkUnknown
-
A. Manzoni HospitalCompleted
-
Peking University First HospitalCompletedInflammation | UremiaChina
-
Assiut UniversityCompleted
-
Università degli Studi di BresciaCompletedDialysis | Uremia | Survival | Elderly (Aged >70) | Low Protein DietItaly