The Acute Effects of Eucaloric and Hypocaloric Carbohydrate Restriction on Liver Fat Content and Metabolism in Obese Individuals (FixedCarb)

The primary aim of this study is to investigate the acute changes in liver fat content in response to a fixed carbohydrate restriction (i.e. intake of 60g/day or 70g/day for women and men, respectively) in individuals with obesity. This will be performed both as 2 days of very low calorie diet (500 and 600 kcal/day for women and men, respectively) and 2 days of eucaloric low carbohydrate diet.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes; Metabolic Syndrome; NAFLD; Overweight and Obesity
• Intervention / Treatment: Other: Dietary composition of macronutrients and calories

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men (30-75 years) and postmenopausal women 45-75 years old
• Hba1c <48 mmol/mol without antidiabetic treatment
• Obese (BMI 27-40 kg/m2)
• Non smokers

Exclusion Criteria:

• Anemia (hemoglobin <8 mmol/L for men and <7 mmol/L for women)
• TSH outside reference range
• Medication known to influence glucose metabolism or appetite regulation
• Contraindications for MR-scan: abdominal height exceed limitations of the MR-scanner, pacemaker or other electronic device implanted, implanted metal devices, severe claustrophobia
• Food allergies (including lactose and gluten intolerance), vegetarian/vegan diet or following specific dietary plans
• Alcohol consumptions >84/168 g/week (women/men)
• Strenuous activity level > 120 minutes per week
• >5 kg weight loss within the last three months or previous bariatric surgery
• High risk of fibrosis of the liver (estimated by FIB4 score > 3,25)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control Arm; 2 days of eucaloric control diet prior to MRS estimating liver fat (control arm)	Other: Dietary composition of macronutrients and calories; Carbohydrate restriction
Experimental: Hypocaloric low carbohydrate; 2 days of eucaloric control diet + 2 days of hypocaloric (500-600 kcal m/f) low carbohydrate diet prior to liver fat estimated by MRS and metabolic testday.	Other: Dietary composition of macronutrients and calories; Carbohydrate restriction
Experimental: Eucaloric low carbohydrate; 2 days of eucaloric control diet + 2 days of eucaloric low carbohydrate diet prior to liver fat estimated by MRS and metabolic testday.	Other: Dietary composition of macronutrients and calories; Carbohydrate restriction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is the 1H-Magnetic Resonance Spectroscopy (MRS) determined liver TG content.	We will compare MRS of liver TG after each of the two interventions (2 days of VLCD or 2 days of LC) with MRS liver TG obtained after 2 days of eucaloric conventional diet.	After 2 days completion of dietary intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Secondary outcomes are fasting and postprandial plasma glucose, insulin, and plasma TG concentrations after 2 days VLCD or LC compared with 2 days of eucaloric conventional diet.	After 2 days completion of dietary intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explorative outcomes	Explorative outcomes are the effects of VLCD and LC on subsequent food intake in response to an ad libitum lunch meal.	After 2 days completion of dietary intervention

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: University of Copenhagen Danish Research Centre for Magnetic Resonance; Nutrition Exercise and sports Copenhagen University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: November 22, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Estimate): December 8, 2022

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Body Weight; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome; Overweight
• Other Study ID Numbers: FixedCarb - H-22035189

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No