Depletion of Liver Fat in Type 2 Diabetes

NCT06211556 | Recruiting DMC

• 1 other identifier: H-23045368
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this randomized trial is to determine whether liver fat depletion via a short-term (i.e., two weeks) very-low calorie diet will restore the normal exercise-induced secretion of a signaling protein (fibroblast growth factor 21) from the liver in people living with type 2 diabetes. Participants will have their liver fat, body composition, and various markers of metabolic health assessed and then will be randomized to either the very-low calorie diet intervention or a free-living control group for two weeks. Upon completion of the two-week intervention period, participants will redo all of the pre-intervention assessments. The changes in the assessments from before vs. after the intervention period will be compared between the two intervention groups (i.e., the very-low calorie diet group vs. the free living control group).

Conditions

Type2diabetes; Obesity

Keywords

VLCD; Exercise; Type 2 diabetes; hepatokines; Hepatic steatosis; Liver fat

Outcome Measures

Primary Outcomes (1)

• Difference in change in FGF21 incremental area-under-the-curve

  The difference in change between groups of FGF21 incremental area-under-the-curve in plasma following an exercise bout (continuous cycling at an intensity equivalent to 60% VO2peak for a gross energy expenditure of \~2500 kJ) from baseline to follow-up.

  4 weeks

Secondary Outcomes (16)

• Difference in change in fasting plasma FGF21

  4 weeks

• Difference in change in liver fat fraction

  4 weeks

• Difference in change in fasting and post exercise plasma adiponectin

  4 weeks

• Difference in change in adipose tissue mRNA targets relating to FGF21 signaling

  4 weeks

• Difference in change in fasting and post exercise plasma glucose

  4 weeks

Other Outcomes (5)

• Difference in change in fatty liver index

  4 weeks

• Difference in change in hepatic steatosis index

  4 weeks

• Difference in change in FIB4 index

  4 weeks

Study Arms (2)

Very-low calorie diet

EXPERIMENTAL

Two weeks of \~800kcal/day

Behavioral: Very-low calorie diet

Free-living control

NO INTERVENTION

No intervention control group

Interventions

Very-low calorie diet BEHAVIORAL

\~800 kcal/day delivered via commercially available diet plan (NUPO).

Also known as: VLCD

Very-low calorie diet

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 30-70 years of age

You may not qualify if:

• Diabetes duration \< 7 years
• Body Mass Index (BMI) ≥ 30 kg/m2 and ≤ 40 kg/m2
• Accepts medical regulation by the study endocrinologist
• Inactivity, defined as \< 1,5 hours of structured physical activity pr. week at moderate intensity and cycling \< 30 minutes/5 km pr. day at moderate intensity (moderate intensity = out of breath but able to speak)
• HbA1c ≥ 75 mmol/mol with no glucose lowering medications
• HbA1c ≥ 64 mmol/mol with mono glucose lowering therapy (if compliant with the prescription)
• HbA1c ≥ 57 mmol/mol with ≥ dual glucose lowering therapy (if compliant with the prescription)
• Diagnosis of Type 1 diabetes, MODY-diabetes, Type 1½ diabetes or LADA-diabetes
• eGFR\<60mL/min (assessed via screening blood sample)
• Treatment with any glucose-lowering medications other than metformin (e.g., insulin (long and/or short acting), sulphonylurea based drugs, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter-2 inhibitors, thiazolidinediones, alpha-glucosidase inhibitors)
• Presence of metal in the body that would contraindicate an MRI scan
• Known or signs of intermediate or severe microvascular complications to diabetes (retino-, neuro- or nephropathy)
• Known cancer
• Lung disease, other than asthma that can be managed with beta2-agonists and does not exhibit seasonal variation
• Known cardiovascular disease

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Diabetesforeningen: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Region Hovedstadens Forskningsfond: collaborator

Study Sites (1)

Rigshospitalet - CFAS

Copenhagen, Capital Region, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Obesity; Motor Activity; Diabetes Mellitus, Type 2; Fatty Liver

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases

Study Officials

• Cody G Durrer, Ph.D.

  Center for Aktiv Sundhed - Rigshospitalet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cody G Durrer, Ph.D.

CONTACT

+4550104538; cody.garett.durrer@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD. Post doc

Model Details: Two arm open-label parallel group randomized controlled trial

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: January 18, 2024
• Study Start: February 1, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)