Fructose is a Metabolic and Inflammatory Pathogenic Factor in Metabolic Dysfunction-associated Steatohepatitis (MASH)

NCT07013916 | Recruiting

• 1 other identifier: 344872
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 2

Brief Summary

MASLD (Metabolic dysfunction-associated steatotic liver disease) is a condition where fat builds up in the liver. It is the most common cause of liver disease worldwide. In some people, the fat can irritate the liver (inflammation) and cause damage. This is a more serious condition called MASH (Metabolic dysfunction-associated steatohepatitis). People with MASH more at risk of liver cirrhosis (advanced scarring in the liver) and liver cancer. It is not fully understood why MASLD becomes MASH, or why this happens in some people but not in others. However, it is known that our diet plays a role. Research shows a diet high in a type of sugar called fructose might make MASLD worse. Fructose is found in fruit, honey and table sugar, and lots of processed food and drinks. The body deals with fructose differently to other sugars, which is why fructose may be a problem. Although scientists have studied the effects of fructose in healthy people, no studies so far have included people with MASH, so it is not known if fructose might make the condition worse. To answer this question, the researchers will conduct a four-week randomised, double-blind study to compare the effects of fructose with another sugar called glucose in 36 people with MASH, 18 people with 'simple' MASLD, and 18 controls without liver disease. Participants will follow a low-sugar diet and, after 14 days on this diet, they will add either a glucose or fructose supplement for another 14 days. Participants will attend 3 study visits, where blood, urine, stool, and saliva samples will be taken. The main question is whether fructose causes more inflammation in people with MASH compared to those with MASLD, or people without liver disease. The researchers will also investigate how fructose affects liver fat content, the gut microbiota, and other processes relevant to MASLD/MASH.

Conditions

MASH - Metabolic Dysfunction-Associated Steatohepatitis; MASH With Fibrosis; Steatosis of Liver

Keywords

fructose; MASH; MASLD; liver; inflammation

Outcome Measures

Primary Outcomes (1)

• Change in plasma glutamate concentration

  Difference in the fructose-induced changes in plasma glutamate concentration in patients with MASH and fibrosis compared to patients with simple steatosis (without fibrosis) or healthy controls.

  Changes from baseline to week 2

Secondary Outcomes (13)

• Plasma metabolome

  Changes from baseline to week 2

• Urine metabolome

  Changes from baseline to week 2

• Plasma glucose

  Changes from baseline to week 2

• Plasma triglycerides

  Changes from baseline to week 2

• Serum insulin

  Changes from baseline to week 2

Other Outcomes (1)

• Genetic variants

  Changes from baseline to week 2

Study Arms (2)

Fructose supplementation

ACTIVE COMPARATOR

Participants will consume 100 g/day of fructose powder administered as two 50g sachets, dissolved in water in addition to following a low-sugar diet

Dietary Supplement: fructose

Glucose supplementation

ACTIVE COMPARATOR

Participants will consume 100 g/day of glucose powder administered as two 50g sachets, dissolved in water in addition to following a low-sugar diet

Dietary Supplement: glucose

Interventions

fructose DIETARY_SUPPLEMENT

Fructose powder

Fructose supplementation

glucose DIETARY_SUPPLEMENT

Glucose powder

Glucose supplementation

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able and willing to give written informed consent
• Age 45-65 at consent
• HbA1c \< 48 mmol/mol
• Overweight and stage I obesity using BMI thresholds adjusted for ethnicity:
• kg/m2 - 32.4kg/m2 in South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean populations
• kg/m2 - 34.9kg/m2 in White populations
• MASH Patients:
• Clinical diagnosis of MASH and F2 - F3 fibrosis:
• Either:
• Liver biopsy within 12 months of baseline
• Or:
• History of histologically-diagnosed MASH with current evidence of fatty liver, AST\>20 and Fibroscan CAP≥248 dB/m and stiffness 9.5kPa -14kPa
• Or:
• FAST score \>0.67
• Patients with steatosis:

You may not qualify if:

• Unwilling or unable to give consent
• Age \<45 or \>65
• Any form of diabetes mellitus
• Currently pregnant
• Known fructose intolerance or food allergy
• Diagnosis of cirrhosis or Fibroscan stiffness \>14kPa
• Current Child-Pugh B/C or episode of decompensation in last year
• Non-MASLD liver disease known to participant (including viral hepatitis, auto-immune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, haemochromatosis, sarcoidosis, cystic fibrosis, sickle cell disease)
• Regular alcohol intake \> 14 units a week for females and \>21 units a week for males (participant-reported)
• Smoking, vaping or use of nicotine-containing products within the last month
• Taking prohibited medication:
• Probiotic or antibiotic use within last 4 weeks (Note: participants will be considered eligible if they have undergone a 4-week washout from probiotics or 4-weeks after discontinuing antibiotic use)
• any oral steroids within the last 6 weeks
• current, or within 3 months, use of immunosuppressive medication
• Amiodarone, nitrofurantoin, or anti-fungals within 3 months

Sponsors & Collaborators

• Queen Mary University of London: lead
• King's College London: collaborator
• University of Surrey: collaborator

Study Sites (2)

Royal London Hospital

London, E1 1FR, United Kingdom

RECRUITING

Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London

London, E1 2AT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Fatty Liver; Inflammation

Interventions

Fructose; Glucose

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Central Study Contacts

William Alazawi, MA(Cantab), MB, PhD

CONTACT

+44 20 7882 7225; w.alazawi@qmul.ac.uk

Olivia Bolton, Masters

CONTACT

+44 20 788 23916; o.bolton@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both participants and members of the research team will be blinded to the intervention allocation (fructose or glucose). The randomisation list will be maintained by an independent researcher with no role in conducting the research.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a four-week randomised double-blind parallel-arm food supplement intervention study that will determine the effect of fructose (arm 1) and glucose (arm 2) on metabolism in people with MASH (n=36), compared to people with simple steatosis (n=18), or controls without liver disease (n=18).

Study Record Dates

• First Submitted: April 28, 2025
• First Posted: June 10, 2025
• Study Start: June 30, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 23, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)