Steatosis of LiverNCT06154096
Liver Fat and Glucagon Resistance
An observational study of Steatosis of Liver, run by Imperial College London.
Trial summary
One in four adults worldwide have too much fat stored in the liver which is known as metabolic associated steatotic liver disease (MASLD). This was previously known as non- alcoholic fatty liver disease (NAFLD). This can lead to liver failure and death in severe cases. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Steatosis of Liver
- What is being tested?
- Acute glucagon infusion
- Type of treatment
- Injection or infusion
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Mar 2024to Sep 2024
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy volunteers and patients with MASLD
Who may be able to join
- Male or female
- Able to give full informed consent
- 18 years old or more (children have different metabolism)
- INCLUSION CRITERIA (healthy volunteers) • Normal FIB4 (<1.3; this indicates no evidence of liver fibrosis)
- Biopsy-proven or clinically diagnosed MASLD (>5% steatosis)
Who cannot join
- Current or history of any medical condition that could interfere with the study or potentially cause harm to the participant
- Pregnant or breastfeeding (affects metabolism)
- Recent weight loss or gain (>10% in previous 3 months)
- History of hypersensitivity to any of the infusates listed in the study design
- Diabetes or pre-diabetes (HbA1C >42mmol/mol)
- Consumption of over 14 units of alcohol per week
Show all 10Show fewer
- Evidence of metabolic syndrome
- Previous or current clinical or biochemical evidence of liver disease
- Evidence of liver cirrhosis
- Non-metabolic associated causes of liver disease (e.g. viral hepatitis)
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Response to Glucagon in Patients With Metabolic-associated Steatotic Liver Disease: a Feasibility Study
One in four adults worldwide have too much fat stored in the liver which is known as metabolic associated steatotic liver disease (MASLD). This was previously known as non- alcoholic fatty liver disease (NAFLD). This can lead to liver failure and death in severe cases. Unfortunately, there are no specific drugs to treat MASLD.
Glucagon is a natural hormone that controls how the body stores and uses fuel. Glucagon acts on liver cells to use protein and fat to make sugar. It decreases the amount of liver fat.
Read more
The investigators think that patients with MASLD may not respond to the actions of glucagon. This could contribute to the build-up of fat in the liver.
In this study the investigators will be investigating the effects of glucagon on protein breakdown and sugar production in patients with and without MASLD.
Healthy volunteers and patients with MASLD will attend for one study visit each which will last for 4-5 hours. During this time they will have infusions into a vein of glucagon and other hormones, amino acids (to mimic the fed state) and 'tracers'. From another vein they will have several blood samples during this period. By analysing these blood samples the investigators will be able to measure the effects of glucagon on protein and glucose turnover (metabolism), and whether this differs between healthy volunteers and those with MASLD.
If the investigators find that patients with MASLD are resistant to the actions of glucagon, this could help with the development of drugs to treat MASLD.
Read the detailed description
This is a feasibility cohort-control experimental medicine study. Participants will attend for one study visit lasting 4-5 hours. The study will involve a maximum of 10 healthy volunteers and 10 patients with MASLD. All subjects will undergo an amino acid infusion and pancreatic clamp during which they will have stable isotope turnover of glucose and alanine measured in two steady state periods - firstly, with low-dose glucagon infusion and secondly, with high-dose glucagon infusion. The studies will take place in the Clinical Research Unit at Hammersmith Hospital, Imperial College.
Screening visit:
During this visit that will last around an hour, prospective participants will have a consultation with a study doctor. The doctor will assess medical history and explain the study. They will also perform a routine physical examination and take some blood tests. Women of child-bearing age will undergo urinalysis to exclude pregnancy. Participants will be contacted a couple of days later to let discuss blood test results, and if these are satisfactory they will be invited to attend for 1 study visit.
Study visit:
Participants will be asked to avoid alcohol and strenuous exercise for 24 hours before the study visit. They will be asked to fast (that is, consume nothing except water) for 10-14 hours before the visit. The visits will start at around 8 or 9am and finish at about 1 or 2pm.
On arrival, female volunteers will be asked for a urine specimen which will be tested for evidence of pregnancy. Participants will be weighed and have pulse, blood pressure and temperature checked.
The participant's arms will be loosely wrapped in a heating pad (50°C). A study investigator will insert two cannulae (thin flexible tubes) into a vein in each arm. One cannula will be used for infusions and the other for blood samples. The investigators will infuse glucagon and two other hormones (insulin and somatostatin), amino acids (to mimic the 'fed state') and 'tracers' of an amino acid called alanine and glucose. The investigators will take multiple blood samples at intervals during the infusions to measure the levels of hormones, sugar and protein in the blood. The total amount will be less than 200ml (around 11 tablespoons), which is less than half the amount taken during a blood donation session.
After 3.5 hours the cannulae will be removed, the participant will be offered something to eat, and after 15-30 minutes of observation they will be allowed to leave the unit. During the study participants can watch TV or read. They will not be able to eat but they can sip water.
- Conditions
- Steatosis of Liver
- Being tested
- Acute glucagon infusion
- Medical subject headings
- Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute glucagon infusionOther
All subjects will undergo an amino acid infusion and pancreatic clamp during which they will have stable isotope turnover of glucose and alanine measured in two steady state periods - firstly, with low-dose glucagon infusion and secondly, with high-dose glucagon infusion
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteer | Subject without MASLD or metabolic-associated disease Receives: Other: Acute glucagon infusion | |
| MASLD | Subject with MASLD Receives: Other: Acute glucagon infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Standard deviation of alanine turnover
Standard deviation of differences in alanine turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Standard deviation of glucose turnover
Standard deviation of differences in glucose turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Secondary outcomes (11)
Plasma glucagon
Differences in plasma glucagon between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma insulin
Differences in plasma insulin between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma lactate
Differences in plasma lactate between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma free fatty acids
Differences in plasma free fatty acids between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma total amino acids
Differences in plasma total amino acids between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma urea
Differences in plasma urea between two steady state periods (low and high dose glucagon infusion) insulin, lactate, free fatty acids, total amino acids and urea between two steady state periods (low and high dose glucagon infusion)
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma metabolite composition
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Urine metabolite composition
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma lipid composition
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Urine lipid composition
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Microbiome composition of stool
Method: sequencing of 16S rRNA
Measured: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2023
- Study startMar 2024 (estimated)
- Primary completionSep 2024 (estimated)
- Study completionSep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Steatosis of LiverStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emma Rose McGlone, PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06154096
- Sponsor's protocol ID
- 334557
- Status last verified
- Nov 2023
- First submitted
- 15 Nov 2023
- Last updated
- 1 Dec 2023
- Results posted
- No
- 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 1 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Response to Glucagon in Patients With Metabolic-associated Steatotic Liver Disease: a Feasibility Study
- ClinicalTrials.gov ID
- NCT06154096
- Acronym / sponsor ID
- 334557
- Conditions
- Steatosis of Liver
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Mar 2024 (estimated)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Sep 2024 (estimated)
- First posted
- 1 Dec 2023 (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.
One in four adults worldwide have too much fat stored in the liver which is known as metabolic associated steatotic liver disease (MASLD). This was previously known as non- alcoholic fatty liver disease (NAFLD). This can lead to liver failure and death in severe cases. Unfortunately, there are no specific drugs to treat MASLD.
Glucagon is a natural hormone that controls how the body stores and uses fuel. Glucagon acts on liver cells to use protein and fat to make sugar. It decreases the amount of liver fat.
The investigators think that patients with MASLD may not respond to the actions of glucagon. This could contribute to the build-up of fat in the liver.
In this study the investigators will be investigating the effects of glucagon on protein breakdown and sugar production in patients with and without MASLD.
Healthy volunteers and patients with MASLD will attend for one study visit each which will last for 4-5 hours. During this time they will have infusions into a vein of glucagon and other hormones, amino acids (to mimic the fed state) and 'tracers'. From another vein they will have several blood samples during this period. By analysing these blood samples the investigators will be able to measure the effects of glucagon on protein and glucose turnover (metabolism), and whether this differs between healthy volunteers and those with MASLD.
If the investigators find that patients with MASLD are resistant to the actions of glucagon, this could help with the development of drugs to treat MASLD.
Detailed description
This is a feasibility cohort-control experimental medicine study. Participants will attend for one study visit lasting 4-5 hours. The study will involve a maximum of 10 healthy volunteers and 10 patients with MASLD. All subjects will undergo an amino acid infusion and pancreatic clamp during which they will have stable isotope turnover of glucose and alanine measured in two steady state periods - firstly, with low-dose glucagon infusion and secondly, with high-dose glucagon infusion. The studies will take place in the Clinical Research Unit at Hammersmith Hospital, Imperial College.
Screening visit:
During this visit that will last around an hour, prospective participants will have a consultation with a study doctor. The doctor will assess medical history and explain the study. They will also perform a routine physical examination and take some blood tests. Women of child-bearing age will undergo urinalysis to exclude pregnancy. Participants will be contacted a couple of days later to let discuss blood test results, and if these are satisfactory they will be invited to attend for 1 study visit.
Study visit:
Participants will be asked to avoid alcohol and strenuous exercise for 24 hours before the study visit. They will be asked to fast (that is, consume nothing except water) for 10-14 hours before the visit. The visits will start at around 8 or 9am and finish at about 1 or 2pm.
On arrival, female volunteers will be asked for a urine specimen which will be tested for evidence of pregnancy. Participants will be weighed and have pulse, blood pressure and temperature checked.
The participant's arms will be loosely wrapped in a heating pad (50°C). A study investigator will insert two cannulae (thin flexible tubes) into a vein in each arm. One cannula will be used for infusions and the other for blood samples. The investigators will infuse glucagon and two other hormones (insulin and somatostatin), amino acids (to mimic the 'fed state') and 'tracers' of an amino acid called alanine and glucose. The investigators will take multiple blood samples at intervals during the infusions to measure the levels of hormones, sugar and protein in the blood. The total amount will be less than 200ml (around 11 tablespoons), which is less than half the amount taken during a blood donation session.
After 3.5 hours the cannulae will be removed, the participant will be offered something to eat, and after 15-30 minutes of observation they will be allowed to leave the unit. During the study participants can watch TV or read. They will not be able to eat but they can sip water.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteer | – | Other: Acute glucagon infusionSubject without MASLD or metabolic-associated disease |
| MASLD | – | Other: Acute glucagon infusionSubject with MASLD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy volunteers and patients with MASLD
Key inclusion criteria (5 listed)
- Male or female
- Able to give full informed consent
- 18 years old or more (children have different metabolism)
- INCLUSION CRITERIA (healthy volunteers) • Normal FIB4 (<1.3; this indicates no evidence of liver fibrosis)
- Biopsy-proven or clinically diagnosed MASLD (>5% steatosis)
Key exclusion criteria (10 listed)
- Current or history of any medical condition that could interfere with the study or potentially cause harm to the participant
- Pregnant or breastfeeding (affects metabolism)
- Recent weight loss or gain (>10% in previous 3 months)
- History of hypersensitivity to any of the infusates listed in the study design
- Diabetes or pre-diabetes (HbA1C >42mmol/mol)
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 |
|---|---|---|
| Acute glucagon infusionAll subjects will undergo an amino acid infusion and pancreatic clamp during which they will have stable isotope turnover of glucose and alanine measured in two steady state periods - firstly, with low-dose glucagon infusion and secondly, with high-dose glucagon infusion | Other | Healthy volunteer, MASLD |
Primary outcome
Standard deviation of alanine turnover
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Standard deviation of differences in alanine turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
Standard deviation of glucose turnover
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Standard deviation of differences in glucose turnover between two steady state periods (low and high dose glucagon infusion) for use in a subsequent sample size calculation
11 secondary outcomes
Plasma glucagon
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma insulin
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma lactate
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma free fatty acids
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma total amino acids
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma urea
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma metabolite composition
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Urine metabolite composition
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Plasma lipid composition
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Urine lipid composition
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Microbiome composition of stool
Time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 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.
Emma Rose McGlone, PhD principal investigator
Imperial College London
Questions about this trial
What is this clinical trial studying?
An observational study of Steatosis of Liver, run by Imperial College London.
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 5 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 1 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Emma Rose McGlone, PhD (+44(0)20 3312 7619, e.mcglone@ic.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Standard deviation of alanine turnover (time frame: one study visit = 1 day per volunteer, 20 study visits, 3 months in total). The study lists 2 primary outcomes in all. 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 1 Dec 2023.