End-stage Renal DiseaseNCT02237521
The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease
An observational study of End-stage Renal Disease, run by Bo Feldt-Rasmussen at 1 site in Denmark.
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… Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- End-stage Renal Disease
- What is being tested?
- Eu- and hyperglycemic clamp and Arginine test
- Type of treatment
- Injection or infusion
- How many people
- 24 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2014to 28 Apr 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 1. End-stage renal disease patients receiving chronic hemodialysis treatments 2. Healthy control subjects
Who may be able to join
- Chronic hemodialysis-dependent uremia in more than 3 months
- Normal kidney function
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- End-stage Renal Disease
- Being tested
- Eu- and hyperglycemic clamp, Arginine test
- Keywords
- Incretin hormones, End-stage renal disease, ESRD, GLP-1, GIP, Insulin, Glucagon
- Medical subject headings
- Kidney Failure, Chronic, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eu- and hyperglycemic clampOther
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 testOther
Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon
| Study group | Role | What they receive |
|---|---|---|
| End-stage renal disease | Patients with normal glucose tolerance and end-stage renal disease Receives: Other: Eu- and hyperglycemic clamp; Other: Arginine test | |
| Controls | Healthy controls with normal kidney function and normal glucose tolerance Receives: Other: Eu- and hyperglycemic clamp; Other: Arginine test |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups
Average plasma insulin concentrations during hyperglycemia
Measured: 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 outcomes (5)
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.
Measured: Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes
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.
Measured: 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
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.
Measured: Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes
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).
Measured: 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
The effect of GLP-1 and GIP on potassium concentrations during euglycemia
Average plasma potassium concentrations during euglycemia
Measured: Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2014 (estimated)
- Study startSep 2014
- Primary completion28 Apr 2016
- Study completion28 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-stage Renal DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bo Feldt-Rasmussen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bo Feldt-Rasmussen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Morten B Jørgensen, MD, Principal investigator, Department of Nephrology, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02237521
- Sponsor's protocol ID
- H-2-2014-021
- Status last verified
- May 2017
- First submitted
- 29 Aug 2014
- Last updated
- 22 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease
- ClinicalTrials.gov ID
- NCT02237521
- Acronym / sponsor ID
- H-2-2014-021
- Conditions
- End-stage Renal Disease
- Keywords
- Incretin hormones, End-stage renal disease, ESRD, GLP-1, GIP, Insulin, Glucagon
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Bo Feldt-RasmussenUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- 28 Apr 2016 (actual)
- Study completion
- 28 Apr 2016 (actual)
- First posted
- 11 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| End-stage renal disease | – | Other: Eu- and hyperglycemic clamp, Other: Arginine testPatients with normal glucose tolerance and end-stage renal disease |
| Controls | – | Other: Eu- and hyperglycemic clamp, Other: Arginine testHealthy controls with normal kidney function and normal glucose tolerance |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 1. End-stage renal disease patients receiving chronic hemodialysis treatments 2. Healthy control subjects
Key inclusion criteria (2 listed)
- Chronic hemodialysis-dependent uremia in more than 3 months
- Normal kidney function
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eu- and hyperglycemic clampEu- 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 | Controls, End-stage renal disease |
| Arginine testBolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon | Other | Controls, End-stage renal disease |
Primary outcome
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
5 secondary outcomes
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
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
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morten B Jørgensen, MD principal investigator
Department of Nephrology, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of End-stage Renal Disease, run by Bo Feldt-Rasmussen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2017.