Clinical trial NCT03401970: Dietary Carbohydrate and Internal Body Fat
Official title: Dietary Carbohydrate and Internal Body Fat Mass in Women and Men With Obesity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Adiposity
Keywords: Body composition
Internal body fat
Dietary pattern
Dietary carbohydrate
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: University of Bergen
First posted: 2018-01-17
Enrollment: 150
Sex: ALL
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 2-year randomized controlled trial to test the effect of dietary carbohydrates, both quality and quantity, on changes in internal body fat mass. Up to 250 women and men with obesity are recruited in Bergen, Norway, and randomized to one of the following normo- and isocaloric dietary patterns (same amount of protein, polyunsaturated fatty acids and moderate energy, 2,000 - 2,500 kcal per day): 1) a low-fat high-carbohydrate diet primarily with refined (e.g., flour-based) carbohydrate sources, 2) a low-fat high-carbohydrate diet based on minimally refined (e.g., cellular) carbohydrate sources, and 3) a very-high-fat low-carbohydrate diet.

Detailed description: Obesity, and high internal fat storage in particular, represents a tremendous and increasing health challenge across the world, and is linked to the recent introduction and globalization of an ultra-processed food supply largely based on refined carbohydrates. However, more high-quality studies are needed to directly assess the role of carbohydrate quality in abdominal adiposity. We also need studies with greater long-term adherence to prescribed food profiles, which may be achievied with the help of new electronic tools such as meal planning applications.

The participants select and plan all meals among a list of carefully designed options, using an application/recipe booklet developed for the study. Each recipe/meal/snack is designed to fully comply with the overall macronutrient- and dietary profile for the respective groups. We will further instruct the participants to record their meal choices during three days every 14 days, and to record all deviations throughout the intervention.

Enrolled participants are invited to study visits at baseline and after 3, 6, 9, 12 and 24 months. At all or some of these time points, the participants provide biological samples (blood, urine and feces, and for some, adipose and/or muscle tissue) and undergo phenotyping, e.g., measurement of body weight and fat mass by bioelectrical impedance analysis and low-radiation CT imaging, and a standardized meal test with blood sample collection up to 4 hours postprandially. In addition, participants will be asked to fill out a collection of questionnaires that assess quality of life, motivation, fatigue, gastrointestinal health, appetite and physical activity. We ask the participants to maintain the same level of physical activity throughout the study.

The primary outcome measure is change in internal body fat mass (visceral adipose tissue) measured by CT imaging. Secondary outcome measures include change in 2-hour postprandial serum concentrations of insulin, change in 4-hour postprandial serum concentrations of triacylglycerols, and change in fecal microbiota composition measured by 16S sequencing.

Eligibility criteria: Inclusion Criteria:

* Body-mass index (BMI) equal to or above 30 kg/m2 and/or waist circumference equal to or above 102 cm for men and 88 cm for women
* Weight stable during the last 2 months before start of the study (less than 5 % change in body weight up or down)
* No known diabetes or consumption of diabetes medication
* Desire to follow a specified dietary pattern using specific recipes throughout the time of the study period
* Ability to periodically record food intake using a specially designed app for the study

Exclusion Criteria:

* Use of statins and/or diabetes medication
* Recent surgical or antibiotics treatment during the last 2 months before start of the study
* Chronic inflammatory bowel disease
* Serious disease
* Smoking
* Pregnancy or breast feeding
* Alcohol consumption during the study of more than 2 alcohol units per day (1 unit = 15 ml (12.8 g) pure alcohol)

Primary outcomes:
measure: Change in internal body fat
timeFrame: Baseline and 6, 12 and 24 months
Secondary outcomes:
measure: Change in postprandial insulin
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in postprandial C-peptide
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in postprandial triacylglycerol
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in postprandial area under the curve (AUC) glucose
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in postprandial non-esterified fatty acids
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fecal microbiome composition
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in liver density
timeFrame: Baseline and 6, 12 and 24 months
measure: Change in pericardial fat mass
timeFrame: Baseline and 6, 12 and 24 months
measure: Change in abdominal subcutaneous fat mass
timeFrame: Baseline and 6, 12 and 24 months
measure: Change in coronary artery calcification (CAC)
timeFrame: Baseline and 6, 12 and 24 months
measure: Change in waist circumference
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in body-mass index
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fasting insulin
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fasting C-peptide
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fasting TAG
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fasting HDL cholesterol
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in TAG/HDL-C ratio
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fasting LDL cholesterol
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in apolipoprotein profile
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in circulating and urine metabolites associated with one-carbon metabolism
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in total fat mass
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in lean mass
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in appetite/fullness
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in gastrointestinal symptoms by the Roma III questionnaire
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in gastrointestinal symptoms by the IBS-SSS questionnaire
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in fatigue
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in perception of health / quality of life
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
measure: Change in quality of life related to gastrointestinal symptoms
timeFrame: Baseline and 3, 6, 9, 12 and 24 months
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Forskningsenhet for helseundersøkelser (research unit for clinical trials), Department of Clinical Science, University of Bergen
Study officials:
affiliation: University of Bergen
name: Simon N Dankel, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Gunnar Mellgren, MD PhD
role: STUDY_DIRECTOR
References:
citation: Sommersten CH, Laupsa-Borge J, Andersen AIO, Fasmer KE, Holmefjord MA, Revheim I, Johannessen KK, Naesheim NT, Storas I, Leikanger T, Amundsen K, Skjerve KL, Lawrence-Archer L, Spjelkavik C, Haldorsen I, Lindseth I, Dierkes J, Mellgren G, Dankel SN. Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity - a randomized controlled trial (CARBFUNC). Clin Nutr. 2022 Oct;41(10):2345-2355. doi: 10.1016/j.clnu.2022.08.028. Epub 2022 Sep 5.