Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02237521
Other study ID # H-2-2014-021
Secondary ID
Status Completed
Phase N/A
First received August 29, 2014
Last updated May 19, 2017
Start date September 2014
Est. completion date April 28, 2016

Study information

Verified date May 2017
Source Rigshospitalet, Denmark
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion, elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play important roles. Our research group has previously found that dialysis patients without type 2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress glucagon after a meal - two early pathophysiological characteristics of patients with T2DM and normal kidney function.

The aim of the project is to provide a detailed description of the mechanisms underlying the (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to investigate the above mentioned disturbances during fasting and hyperglycaemic conditions using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will be used to determine the effect of the incretin hormones on the endogenous glucose handling.

We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect to healthy control subjects.


Description:

The effect of the incretin hormones on the endocrine pancreatic function in a uremic environment will be explored during fasting and hyperglycemic conditions in three randomised examination days.

At a preceding screening day, an oral glucose tolerance test (OGTT) and a dual energy x-ray absorptiometry (DXA) scan will be performed to determine glucose tolerance and the distribution of muscle and adipose tissue. The study will be carried out on three separate days differing with respect to the hormones infused: GLP-1, GIP or placebo (saline) which are double blinded. The patients will meet from an overnight fast and an infusion of one of the hormones is initiated. At the same time labeled glucose will be infused to determine the endogenous hepatic glucose production. A glucose infusion is adjusted according to frequent plasma glucose measurements to maintain fasting glucose level. After 2 hours a steady state of the tracer is achieved and a 2 hour hyperglycemic clamp, 3 mmol/l above fasting glucose concentration will be started. The tracer infusions are continued during the hyperglycemia. After the 4 hour clamp an arginine bolus will be administered to measure the ability to increase the secretion of insulin and glucagon.


Recruitment information / eligibility

Status Completed
Enrollment 24
Est. completion date April 28, 2016
Est. primary completion date April 28, 2016
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria (End-stage renal disease):

- Chronic hemodialysis-dependent uremia in more than 3 months

Inclusion Criteria (Healthy controls):

- Normal kidney function

Exclusion Criteria:

- Fasting plasma glucose = 6.1 mmol/l

- 2h plasma glucose = 7.8 after ingestion of 75 grams of glucose

- Admittance to a hospital

- Anemia (Hb < 6.0 mmol/l)

- Ongoing treatment with drugs interfering with glucose metabolism including steroids and calcineurin inhibitors

- Bowel resection or any other large abdominal surgery

Study Design


Intervention

Other:
Eu- and hyperglycemic clamp
Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.
Arginine test
Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Locations

Country Name City State
Denmark Department of Nephrology, Rigshospitalet Copenhagen

Sponsors (1)

Lead Sponsor Collaborator
Bo Feldt-Rasmussen

Country where clinical trial is conducted

Denmark, 

Outcome

Type Measure Description Time frame Safety issue
Primary The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups Average plasma insulin concentrations during hyperglycemia Average during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes
Secondary The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during euglycemia. Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes
Secondary The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during the first 10 minutes and last 30 minutes of hyperglycemia. Averages during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes
Secondary The effect of GLP-1 and GIP on insulin and glucagon response to arginine Average plasma insulin and glucagon concentrations 10 minutes following arginine bolus at the end of the examination. Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes
Secondary The effect of GLP-1 and GIP on the peripheral glucose handling Average glucose infusion rate during both euglycemia (the first 2 hours) and hyperglycemia (the last 2 hours). Average during the first 4 hours of each examination day. Blood samples are collected at 5-15 minutes interval from time 0 to time 240 minutes
Secondary The effect of GLP-1 and GIP on potassium concentrations during euglycemia Average plasma potassium concentrations during euglycemia Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes
See also
  Status Clinical Trial Phase
Completed NCT04087213 - Study of HemoCareā„¢ Hemodialysis System for Home Nocturnal Dialysis in Patients With ESRD N/A
Completed NCT02207088 - Ombitasvir/ABT-450/Ritonavir and Dasabuvir With or Without Ribavirin in HCV Genotype 1-Infected Adults With Chronic Kidney Disease Phase 3
Not yet recruiting NCT03090828 - Economic Evaluation of an Education Platform for Patients With End-stage Renal Disease N/A
Withdrawn NCT01691196 - Inflammation in Peritoneal Dialysis Patients: Effect of Obesity
Completed NCT01394341 - Liraglutide Treatment to Patients With Severe Renal Insufficiency Phase 4
Active, not recruiting NCT00247507 - The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients Phase 4
Completed NCT00307463 - Effects of Strict Volume Control in Hypertensive Hemodialysis Patients on Cardiac Structure and Chronic Inflammation Phase 4
Recruiting NCT00155363 - Effect of Different Hemodialysis Modality on Adiponectin,Vascular Function and Clinical Prognosis Phase 4
Completed NCT00234156 - The Effect of Fructose on Blood Fats in Dialysis Patients and Healthy Volunteers N/A
Completed NCT00586131 - Arterial pH and Total Body Nitrogen Balances in APD Phase 4
Active, not recruiting NCT05027074 - Global Study of MK-2060 (Anti-Factor XI Monoclonal Antibody) in Participants With End Stage Renal Disease Receiving Hemodialysis (FXI Hemodialysis Study) (MK-2060-007) Phase 2
Recruiting NCT04575077 - The Role of Hepcidin as a Biomarker to Predict Successful Renal Transplantation
Enrolling by invitation NCT05001009 - Goals of Care Conversations Study N/A
Completed NCT01756508 - Eculizumab for Prevention and Treatment of Kidney Graft Reperfusion Injury Phase 2
Recruiting NCT03862859 - The Danish Warfarin-Dialysis Study - Safety and Efficacy of Warfarin in Patients With Atrial Fibrillation on Dialysis Phase 4
Terminated NCT03661229 - Cardiovascular and Respiratory Assessment Using Biometric Signals in a Non-contact Monitoring Device N/A
Completed NCT03288922 - Protein-bound Toxin Removal Between Limited Blood Flow Super High-flux Online HDF and High-Efficiency Online HDF N/A
Completed NCT02360748 - A Plant Based High Protein Diet to Improve Nutritional Outcomes in Peritoneal Dialysis Patients N/A
Completed NCT02572882 - Gut Microbiome and p-Inulin in Hemodialysis N/A
Not yet recruiting NCT02238093 - Cardiorenal Syndrome in End-Stage Kidney Disease N/A