Dietary Carbohydrate and Internal Body Fat

Adiposity Clinical Trial

— CARBFUNC  

Official title:

Dietary Carbohydrate and Internal Body Fat Mass in Women and Men With Obesity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03401970
• Other study ID #: 2017/621
• Status: Completed
• Phase: N/A
• Start date: January 3, 2018
• Est. completion date: March 24, 2021

Study information

• Verified date: April 2021
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 24, 2021
• Est. primary completion date: May 20, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Adiposity
• Obesity

Intervention

Behavioral:
• Acellular carbohydrate diet
Participants will be asked to consume 2,000 - 2,500 kcals, thereof 45 energy percent (E%) carbohydrate (up to 5 E% added sugar), 30 E% fat (10-12 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.
• Cellular carbohydrate diet
Participants will be asked to consume 2,000 - 2,500 kcals, thereof 45 energy percent (E%) carbohydrate (up to 1 E% added sugar), 38 E% fat (10-12 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.
• Low-carbohydrate high-fat diet
Participants will be asked to consume 2,000 - 2,500 kcals, thereof 10 energy percent (E%) carbohydrate (up to 1 E% added sugar), 73 E% fat (30 E% saturated fatty acids and 7-10 E% polyunsaturated fatty acids) and 17 E% protein. They will use an original online/smartphone application that provides choices of meals/food combinations/recipes corresponding to their prescribed macronutrient profile and dietary pattern. Participants are asked to complete 3-day dietary records every 14 days throughout the study, and to report any deviations from the planned interventions.

Locations

Country	Name	City	State
Norway	Forskningsenhet for helseundersøkelser (research unit for clinical trials), Department of Clinical Science, University of Bergen	Bergen

Sponsors (2)

Lead Sponsor	Collaborator
Haukeland University Hospital	University of Bergen

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in internal body fat	Visceral fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Secondary	Change in postprandial insulin	Circulating insulin concentrations measured before and 2 hours after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in postprandial C-peptide	Circulating C-peptide concentrations measured before and 2 hours after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in postprandial triacylglycerol	Triacylglycerol concentrations measured before and 4 hours after intake of a mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in postprandial area under the curve (AUC) glucose	Circulating glucose measured before and after 30, 60, 90, 120 and 240 minutes after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in postprandial non-esterified fatty acids	Circulating non-esterified fatty acid concentrations before and after 60, 120 and 240 minutes after intake of a standardized mixed meal	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fecal microbiome composition	Microbiome composition measured by 16S sequencing	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in liver density	Calculated as liver/spleen attenuation index (Hounsfield units) based on quantification by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Secondary	Change in pericardial fat mass	Pericardial fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Secondary	Change in abdominal subcutaneous fat mass	Abdominal subcutaneous fat mass (cm3) measured by computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Secondary	Change in coronary artery calcification (CAC)	CAC score calculated based on computed tomography (CT) imaging	Baseline and 6, 12 and 24 months
Secondary	Change in waist circumference	Waist circumference (cm) measured by a measuring tape	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in body-mass index	Body-mass index measured as body weight (kg) divided by height (m) squared	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fasting insulin	Circulating fasting insulin concentrations	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fasting C-peptide	Circulating fasting C-peptide concentrations	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fasting TAG	Circulating fasting triacylglycerol concentrations	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fasting HDL cholesterol	Circulating fasting high-density lipoprotein cholesterol (HDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in TAG/HDL-C ratio	The ratio of circulating fasting triacylglycerol (TAG) and high-density lipoprotein cholesterol (HDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fasting LDL cholesterol	Circulating fasting low-density lipoprotein cholesterol (LDL-C)	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in apolipoprotein profile	Circulating fasting apolipoprotein profile measured by multiplex ELISA	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in circulating and urine metabolites associated with one-carbon metabolism	Circulating metabolites in the serine, glycine and histidine pathways measured in the fasted state by GC-MS/MS	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in total fat mass	Total fat mass measured by bioimpedance analysis (BIA)	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in lean mass	Lean mass will be measured by bioimpedance analysis (BIA)	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in appetite/fullness	Subjective appetite and fullness assessed and quantified by the VAS questionnaire	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in gastrointestinal symptoms by the Roma III questionnaire	Gastrointestinal health will be surveyed and quantified by a questionnaire (Rome III Diagnostic Criteria for Irritable Bowel Syndrome (IBS)). The questionnaire surveys criteria for diagnosis of IBS within a 12-week period. The criteria for IBS are based on recurrent abdominal pain or discomfort, 3 days per month in the last 3 months (12 weeks), associated with =2 of the following criteria: 1.Improvement with defecation; 2. Onset associated with a change in stool frequency; 3. Onset associated with a change in stool form (appearance). The criteria are fulfilled with symptoms onset 6 months prior to diagnosis.	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in gastrointestinal symptoms by the IBS-SSS questionnaire	Gastrointestinal health will be surveyed by the IBS-SSS questionnaire. Scores on the IBS-SSS range from 0 to 500 with higher scores indicating more severe symptoms. Subjects can be categorized as having mild (75-175), moderate (175-300), or severe (>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement. Each question on the VAS ranges from 0-100mm, where higher score indicates more severe symptoms.; The categorization based on scores (total possible score = 500) are as follows: 0-75 = not IBS 75-175= mild IBS 175-300 = moderate IBS 300-500 = severe IBS	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in fatigue	The Fatigue Impact Scale will be used to compute a total score for fatigue by summing up the scores for subclasses as follows: cognitive functioning (10 items, subscale range: 0-40), physical functioning (10 items, subscale range: 0-40), and psychosocial functioning (20 items, subscale range: 0-80). The statements are ranged on a five-level scale (0 = no problem to 4 = extreme problems), giving a maximum total FIS score of 160 (total scale range: 0-160) where low scores indicate less fatigue-related issues.	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in perception of health / quality of life	Obesity-specific quality of life is measured with "Patient-Reported Outcomes in Obesity" (PROS), which consists of 8 items tapping how different life domains are affected by obesity. PROS have one overall score, ranging from 0 (optimal) to 3 (poorest).; Generic health-related quality of life is measured with RAND-36, which consists of dimensions ranging from 0 (poorest) to 100 (optimal). There are 8 subscales; physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning and mental health. In addition, RAND-36 also have 2 summary scores: the physical component summary (PCS) (tapping from physical functioning, physical role functioning, bodily pain and general health) and mental component summary (MCS) (tapping from vitality, social functioning, emotional role functioning and mental health).	Baseline and 3, 6, 9, 12 and 24 months
Secondary	Change in quality of life related to gastrointestinal symptoms	The SF-NDI (Short-Form Nepean Dyspepsia Index (SF-NDI)) questionnaire will be used to assess quality of life / psychological wellbeing related to gastrointestinal symptoms. The 10-item SF-NDI was constructed and validated in patients with functional gastrointestinal disorders for measuring health-related quality of life. The 10-item short form includes five subscales: tension, interference with daily activities, eating/drinking, knowledge/control, and work/study, and each subscale contains two items. The items were measured by a 5-point graded Likert scale from 1 to 5. A total sum score for quality of life and a sum score for each of the five subscales were calculated by adding up scores for each item (range of total quality of life, 10-50; range of each subscale, 2-10). Higher scores indicate worse functioning or symptoms.	Baseline and 3, 6, 9, 12 and 24 months