We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02237521
Recruitment Status : Completed
First Posted : September 11, 2014
Last Update Posted : May 22, 2017
Sponsor:
Information provided by (Responsible Party):
Bo Feldt-Rasmussen, Rigshospitalet, Denmark

Brief 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.


Condition or disease Intervention/treatment
End-stage Renal Disease Other: Eu- and hyperglycemic clamp Other: Arginine test

Detailed 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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 24 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Study Start Date : September 2014
Actual Primary Completion Date : April 28, 2016
Actual Study Completion Date : April 28, 2016


Group/Cohort Intervention/treatment
End-stage renal disease
Patients with normal glucose tolerance and end-stage renal disease
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.

Other: Arginine test
Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon

Controls
Healthy controls with normal kidney function and normal glucose tolerance
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.

Other: Arginine test
Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon




Primary Outcome Measures :
  1. The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups [ Time Frame: 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 ]
    Average plasma insulin concentrations during hyperglycemia


Secondary Outcome Measures :
  1. The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia [ Time Frame: Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes ]
    Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during euglycemia.

  2. The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia [ Time Frame: 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 ]
    Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during the first 10 minutes and last 30 minutes of hyperglycemia.

  3. The effect of GLP-1 and GIP on insulin and glucagon response to arginine [ Time Frame: Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes ]
    Average plasma insulin and glucagon concentrations 10 minutes following arginine bolus at the end of the examination.

  4. The effect of GLP-1 and GIP on the peripheral glucose handling [ Time Frame: 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 ]
    Average glucose infusion rate during both euglycemia (the first 2 hours) and hyperglycemia (the last 2 hours).

  5. The effect of GLP-1 and GIP on potassium concentrations during euglycemia [ Time Frame: Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes ]
    Average plasma potassium concentrations during euglycemia


Biospecimen Retention:   Samples With DNA
Serum, plasma and urine


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
  1. End-stage renal disease patients receiving chronic hemodialysis treatments
  2. Healthy control subjects
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02237521


Locations
Layout table for location information
Denmark
Department of Nephrology, Rigshospitalet
Copenhagen, Denmark, 2100
Sponsors and Collaborators
Bo Feldt-Rasmussen
Investigators
Layout table for investigator information
Principal Investigator: Morten B Jørgensen, MD Department of Nephrology, Rigshospitalet
Layout table for additonal information
Responsible Party: Bo Feldt-Rasmussen, MD DMSc, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02237521    
Other Study ID Numbers: H-2-2014-021
First Posted: September 11, 2014    Key Record Dates
Last Update Posted: May 22, 2017
Last Verified: May 2017
Keywords provided by Bo Feldt-Rasmussen, Rigshospitalet, Denmark:
Incretin hormones
End-stage renal disease
ESRD
GLP-1
GIP
Insulin
Glucagon
Additional relevant MeSH terms:
Layout table for MeSH terms
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency