Non-Alcoholic Fatty Liver DiseaseNCT03526445
Hepatic Metabolic Changes in Response to Glucagon Infusion
A study testing Glucagon and Saline in people with Non-Alcoholic Fatty Liver Disease and Total Pancreatectomy, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
The objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure. Read more about this study
- Who is it for?
- Ages 30 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Total Pancreatectomy, Diabetes Mellitus
- What is being tested?
- Glucagon and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteDenmark
- Study dates
- 1 May 2018to 12 Jun 2019
- 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 30 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Pancreatectomised patients
- Patients who have undergone total pancreatectomy
- Caucasian between 30-80
- Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
- Informed consent
- Patients with type 1 diabetes
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- Patients with C-peptide negative type 1 diabetes
- Caucasian between 30-80
- Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
- Informed consent
- Healthy controls
- Normal fasting plasma glucose (< 7 mmol/l) and normal HbA1c (< 6.5 %) (30,31)
- Normal blood haemoglobin (>8.3 mmol/l for males and >7.3 mmol/l for females)
- Caucasian between 30-80
- Informed consent
Who cannot join
- All subjects
- Inflammatory bowel disease
- Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
- Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
- Known liver disease (excluding non-alcoholic fatty liver disease)
- Severe lung disease
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- Pregnancy and/or breastfeeding
- Uncontrolled hypertension and/or significant cardiovascular disease
- Treatment with drugs with potential steatogenic side-effects within three months prior to inclusion
- Alcohol consumption above 21 units/week for men and 14 units/week for women
- Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen
Hellerup, 2900
About this study
The objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure.
Read the detailed description
Most research has focused on the role of the pancreatic hormone, insulin, and insulin signalling (or lack of) in the development of NAFLD. However, increasing evidence suggest that the other major gluco-regulatory pancreatic hormone glucagon is also implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This, combined with observations of increased degree of hepatic steatosis in patients after total pancreatectomy, who are devoid of pancreatic glucagon and typically are lean and peripherally insulin sensitive, suggests that glucagon may play a hitherto unrecognised role in the pathophysiology of NAFLD.
The hypothesis of the study is that exogenously delivered glucagon will drive hepatic metabolism in a lipolytic direction and increase resting energy expenditure without affecting appetite and food intake.
The acute effects of exogeneous glucagon infusion on hepatic lipid metabolism will be evaluated in patients after total pancreatectomy (no endogenous pancreatic hormones), in patients with type 1 diabetes (no endogenous insulin production) and in healthy controls (preserved endogenous pancreatic hormones).
- Being tested
- Glucagon, Saline
- Keywords
- Glucagon, Stable isotope, Energy expenditure, Lipid metabolism, Glucose metabolism, Appetite
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucagonDrug
Also called GlucaGen
Glucagon (4 ng/kg/min)
SalineDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Glucagon | Active comparator | 3 hours i.v. infusion of Glucagon (4 ng/kg/min). Receives: Drug: Glucagon |
| Saline | Placebo comparator | 3 hours i.v. infusion of saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic lipid metabolism
evaluated using isotopic labelled tracer kinetics: lipolysis, ketogenesis, very low-density lipoprotein (VLDL) secretion and free fatty acid (FFA) re-esterification rate
Measured: -120,-30,-15,0,30,60,90,120,135,150 minutes
Secondary outcomes (7)
Changes in plasma concentration of lipids
Total cholesterol, VLDL, LDL, HDL, FFA
Measured: 0, 60,150 minutes
Changes in plasma concentration of amino acids
Measured: 0, 60, 120, 150 minutes
Changes in plasma concentration of fibroblast growth factor 21 (FGF-21)
Measured: -120,0,150 minutes
Endogenous glucose production
Measured by glucose tracer
Measured: -120,-30,-15,0,30,60,90,120,135,150 minutes
Changes in resting energy expenditure and oxidation rate
Measured by indirect calorimetry
Measured: 0, 150 minutes
Food intake
Ad libitum meal
Measured: 30 minutes (150-180) minutes
Changes in appetite sensation
Visual analogue scale
Measured: 0,30,60,90,120,150 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start1 May 2018
- Primary completion12 Jun 2019
- Study completion12 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Alcoholic Fatty Liver 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Sponsor
- Investigators
- Filip Krag Knop, Prof., Study director, Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03526445
- Sponsor's protocol ID
- H-18003696
- Status last verified
- May 2018
- First submitted
- 3 May 2018
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatic Metabolic Changes in Response to Glucagon Infusion
- ClinicalTrials.gov ID
- NCT03526445
- Acronym / sponsor ID
- H-18003696
- Keywords
- Glucagon, Stable isotope, Energy expenditure, Lipid metabolism, Glucose metabolism, Appetite
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 1 May 2018 (actual)
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 12 Jun 2019 (actual)
- First posted
- 16 May 2018 (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 objective of the study is to investigate how exogenously administered glucagon affects hepatic lipid, glucose and protein metabolism as well as appetite, food intake and resting energy expenditure.
Detailed description
Most research has focused on the role of the pancreatic hormone, insulin, and insulin signalling (or lack of) in the development of NAFLD. However, increasing evidence suggest that the other major gluco-regulatory pancreatic hormone glucagon is also implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This, combined with observations of increased degree of hepatic steatosis in patients after total pancreatectomy, who are devoid of pancreatic glucagon and typically are lean and peripherally insulin sensitive, suggests that glucagon may play a hitherto unrecognised role in the pathophysiology of NAFLD.
The hypothesis of the study is that exogenously delivered glucagon will drive hepatic metabolism in a lipolytic direction and increase resting energy expenditure without affecting appetite and food intake.
The acute effects of exogeneous glucagon infusion on hepatic lipid metabolism will be evaluated in patients after total pancreatectomy (no endogenous pancreatic hormones), in patients with type 1 diabetes (no endogenous insulin production) and in healthy controls (preserved endogenous pancreatic hormones).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glucagon | Active comparator | Drug: Glucagon3 hours i.v. infusion of Glucagon (4 ng/kg/min). |
| Saline | Placebo comparator | Drug: Saline3 hours i.v. infusion of saline |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Pancreatectomised patients
- Patients who have undergone total pancreatectomy
- Caucasian between 30-80
- Blood haemoglobin >7.0 mmol/l for males and >6.5 mmol/l for females
- Informed consent
Key exclusion criteria (11 listed)
- All subjects
- Inflammatory bowel disease
- Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
- Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
- Known liver disease (excluding non-alcoholic fatty liver 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 |
|---|---|---|
| GlucagonAlso: GlucaGenGlucagon (4 ng/kg/min) | Drug | Glucagon |
| SalinePlacebo | Drug | Saline |
Primary outcome
Hepatic lipid metabolism
Time frame: -120,-30,-15,0,30,60,90,120,135,150 minutes
evaluated using isotopic labelled tracer kinetics: lipolysis, ketogenesis, very low-density lipoprotein (VLDL) secretion and free fatty acid (FFA) re-esterification rate
7 secondary outcomes
Changes in plasma concentration of lipids
Time frame: 0, 60,150 minutes
Changes in plasma concentration of amino acids
Time frame: 0, 60, 120, 150 minutes
Changes in plasma concentration of fibroblast growth factor 21 (FGF-21)
Time frame: -120,0,150 minutes
Endogenous glucose production
Time frame: -120,-30,-15,0,30,60,90,120,135,150 minutes
Changes in resting energy expenditure and oxidation rate
Time frame: 0, 150 minutes
Food intake
Time frame: 30 minutes (150-180) minutes
Changes in appetite sensation
Time frame: 0,30,60,90,120,150 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 6 Aug 2019.
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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 Krag Knop, Prof. study director
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen
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 and Saline in people with Non-Alcoholic Fatty Liver Disease and Total Pancreatectomy, run by Steno Diabetes Center 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 6 Aug 2019. 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. Some participants in this study may receive a placebo. 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?
Hepatic lipid metabolism (time frame: -120,-30,-15,0,30,60,90,120,135,150 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 6 Aug 2019.