Chronic Kidney DiseasesMCR_EndCirNCT05056584
The Role of the Kidneys and Liver in the Elimination of Glucagon
A study testing Glucagon infusion and Primed tracer infusion in people with Chronic Kidney Diseases and Liver Cirrhosis, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial summary
The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Kidney Diseases, Liver Cirrhosis, Hyperglucagonemia
- What is being tested?
- Glucagon infusion and Primed tracer infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Aug 2020to 28 Mar 2023
- Phase
- Interventional
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The CKD group
- Men/women between 18 and 75 years of age
- CKD stage 4 or 5
- Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range,
- Informed consent
- The cirrhosis group
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- Men/women between 18 and 75 years of age
- Verified diagnosis of cirrhosis - Child-Pugh Score of 5-12
- Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)
- Informed consent
- The control group
- Men/women between 18 and 75 years of age
- Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)(plasma creatinine ≤105 micromol/L (µM) for men and ≤90 µM for women)
- Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range
- Informed consent
Who cannot join
- All groups
- Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l.
- Previous kidney transplantation with remaining kidney graft
- Present treatment with oral glucocorticoids
- Polycystic kidney disease
- Pregnancy or breastfeeding
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- Inflammatory bowel disease
- Surgical procedure within the last 3 months
- Haemoglobin < 6 mmol/l (women) or < 7 mmol/l (men)
- First-degree relatives with diabetes
- Any condition that the investigators feel would interfere with trial participation
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Department of Medicine, Gentofte Hospital
Hellerup, Copenhagen, 2900
About this study
Official title: The Role of the Kidneys and Liver in the Elimination of Glucagon An Evaluation of the Metabolic Clearance Rate of Glucagon in Patients With End-stage Renal Disease and Patients With Liver Cirrhosis
The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.
Read the detailed description
In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism.
The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.
- Conditions
- Chronic Kidney Diseases, Liver Cirrhosis, Hyperglucagonemia
- Being tested
- Glucagon infusion, Primed tracer infusion
- Keywords
- Metabolic clearance rate, Glucagon pharmacodynamics, Glucagon pharmacokinetics
- Medical subject headings
- Renal Insufficiency, Chronic, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon infusionBiological
One hour glucagon-clamp followed by one hour of blood sampling
Primed tracer infusionBiological
Infusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day,
| Study group | Role | What they receive |
|---|---|---|
| Healthy control subjects | Experimental | Healthy control subjects, matched for age, sex and BMI Receives: Biological: Glucagon infusion; Biological: Primed tracer infusion |
| Patients with End-stage Renal Disease | Experimental | Patients with hemodialysis-treated ESRD. Receives: Biological: Glucagon infusion; Biological: Primed tracer infusion |
| Patients with liver cirrhosis | Experimental | Patients with Child-Pugh A or B Cirrhosis Receives: Biological: Glucagon infusion; Biological: Primed tracer infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic clearance rate of glucagon
Glucagon plasma concentration steady state glucagon concentrations
Measured: t = 50 minutes
Secondary outcomes (11)
Glucagon pharmacokinetic 1
Elimination half-life
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacokinetic 2
volume of distribution of Glucagon
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacodynamic - amino acids
Effect of glucagon on amino acid plasma levels before, during and after infusion
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacodynamic - glucose
Effect of glucagon on plasma glucose levels before, during and after infusion
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Tracers
Tracer-to-tracee ratio of labelled isotopes
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120
Insulin
Excursions of plasma concentrations of insulin
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon-like peptide 1
Excursions of plasma concentrations of GLP-1
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Lipid metabolism
Effect of glucagon on lipid metabolism, through lipidomics
Measured: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Vital parameter 1
Systolic blood pressure
Measured: -120, -30, 0, 60, 120 minutes
Vital parameter 2
Diastolic blood pressure
Measured: -120, -30, 0, 60, 120 minutes
Vital parameter 3
Heart rate
Measured: -120, -30, 0, 60, 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2021
- Study start1 Aug 2020
- Primary completion28 Mar 2023
- Study completion28 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Responsible party
- Principal investigator, Magnus Frederik Gluud Grøndahl, University Hospital, Gentofte, Copenhagen
- Investigators
- Filip K Knop, MD, PhD, Study director, Center for Metabolic Research, Gentofte HospitalMagnus FG Grøndahl, MD, Principal investigator, Center for Metabolic Research, Gentofte Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05056584
- Sponsor's protocol ID
- H-16043802
- Acronym
- MCR_EndCir
- Status last verified
- May 2023
- First submitted
- 9 Nov 2020
- Last updated
- 12 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of the Kidneys and Liver in the Elimination of Glucagon An Evaluation of the Metabolic Clearance Rate of Glucagon in Patients With End-stage Renal Disease and Patients With Liver Cirrhosis
- ClinicalTrials.gov ID
- NCT05056584
- Acronym / sponsor ID
- MCR_EndCir / H-16043802
- Conditions
- Chronic Kidney Diseases, Liver Cirrhosis, Hyperglucagonemia
- Keywords
- Metabolic clearance rate, Glucagon pharmacodynamics, Glucagon pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Collaborators
- The Novo Nordisk Foundation Center for Basic Metabolic Research
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 28 Mar 2023 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 24 Sep 2021 (actual)
- 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.
The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.
Detailed description
In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism.
The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy control subjects | Experimental | Biological: Glucagon infusion, Biological: Primed tracer infusionHealthy control subjects, matched for age, sex and BMI |
| Patients with End-stage Renal Disease | Experimental | Biological: Glucagon infusion, Biological: Primed tracer infusionPatients with hemodialysis-treated ESRD. |
| Patients with liver cirrhosis | Experimental | Biological: Glucagon infusion, Biological: Primed tracer infusionPatients with Child-Pugh A or B Cirrhosis |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- The CKD group
- Men/women between 18 and 75 years of age
- CKD stage 4 or 5
- Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range,
- Informed consent
Key exclusion criteria (11 listed)
- All groups
- Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l.
- Previous kidney transplantation with remaining kidney graft
- Present treatment with oral glucocorticoids
- Polycystic kidney disease
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 |
|---|---|---|
| Glucagon infusionOne hour glucagon-clamp followed by one hour of blood sampling | Biological | Healthy control subjects, Patients with End-stage Renal Disease, Patients with liver cirrhosis |
| Primed tracer infusionInfusion of primed isotopically labelled glucose, amino acids and lipids. From 2 hours prior to glucagon infusion and throughout the test day, | Biological | Healthy control subjects, Patients with End-stage Renal Disease, Patients with liver cirrhosis |
Primary outcome
Metabolic clearance rate of glucagon
Time frame: t = 50 minutes
Glucagon plasma concentration steady state glucagon concentrations
11 secondary outcomes
Glucagon pharmacokinetic 1
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacokinetic 2
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacodynamic - amino acids
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon pharmacodynamic - glucose
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Tracers
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120
Insulin
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Glucagon-like peptide 1
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Lipid metabolism
Time frame: -120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes
Vital parameter 1
Time frame: -120, -30, 0, 60, 120 minutes
Vital parameter 2
Time frame: -120, -30, 0, 60, 120 minutes
Vital parameter 3
Time frame: -120, -30, 0, 60, 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 12 May 2023.
- Individual participant dataSharing planned: No
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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.
Filip K Knop, MD, PhD study director
Center for Metabolic Research, Gentofte Hospital
Magnus FG Grøndahl, MD principal investigator
Center for Metabolic Research, Gentofte Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Glucagon infusion and Primed tracer infusion in people with Chronic Kidney Diseases and Liver Cirrhosis, run by University Hospital, Gentofte, Copenhagen 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 15 inclusion and 11 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 12 May 2023. 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?
Metabolic clearance rate of glucagon (time frame: t = 50 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 12 May 2023.