Liver Fat and Glucagon Resistance

NCT06154096 | Unknown

• 1 other identifier: 334557
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Steatosis of Liver

Outcome Measures

Primary Outcomes (2)

• 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

  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

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

Secondary Outcomes (11)

• Plasma glucagon

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

• Plasma insulin

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

• Plasma lactate

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

• Plasma free fatty acids

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

• Plasma total amino acids

  one study visit = 1 day per volunteer, 20 study visits, 3 months in total

Study Arms (2)

Healthy volunteer

Subject without MASLD or metabolic-associated disease

Other: Acute glucagon infusion

MASLD

Subject with MASLD

Other: Acute glucagon infusion

Interventions

Acute glucagon infusion OTHER

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

Healthy volunteer; MASLD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers and patients with MASLD

You may qualify if:

• Male or female
• Able to give full informed consent
• years old or more (children have different metabolism)
• Biopsy-proven or clinically diagnosed MASLD (\>5% steatosis)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Imperial College London: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, faeces, urine

MeSH Terms

Conditions

Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Emma Rose McGlone, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emma Rose McGlone, PhD

CONTACT

+44(0)20 3312 7619; e.mcglone@ic.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2023
• First Posted: December 1, 2023
• Study Start: March 1, 2024
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share