CALIBER Phase 1: A Pilot Study in Normal-weight and Overweight Adults.

Study Overview
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Brief Summary
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Pilot study to compare the impact of following a low-carbohydrate, high-fat diet versus following a high-carbohydrates, moderate-fat diet (UK dietary guidelines) on cardiometabolic risk markers and associated behaviours in a normal-weight and overweight adult population.

Detailed Description
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Cardiometabolic diseases (CMD), such as type 2 diabetes and cardiovascular disease (CVD), are globally amongst the highest contributors to morbidity and mortality with high (cost) implications to the overall economy and health care systems. A number of risk markers have been associated with CMDs, including blood serum markers, low levels of lean mass and high levels of body fat, including increased waist circumference. Dietary factors and nutritional status have long been linked with specific markers of cardiometabolic (CM) risk. The quantity and quality of dietary carbohydrates has been associated with increased serum triglycerides levels, increased body fat mass, increased waist circumference and visceral fat around the organs in particular. They also seem to increase food cravings. Whilst official dietary guidelines in the UK and elsewhere still recommend a high carbohydrate and low fat diet as standard, these recommendations have increasingly been challenged. Evidence has been mounting that very-low carbohydrate (ketogenic) and low carbohydrate diets can ameliorate CM risk factors, especially when a personalised rather than a one-size-fits-all approach is being taken. Response to carbohydrate load and adherence to dietary interventions can vary widely dependent on individual substrate and energy metabolism and insulin-resistant status. The majority of dietary interventions with ketogenic and low-carbohydrate diets has focused on weight loss as the primary outcome in overweight and obese individuals. However, in recent years evidence has been mounting that the location and quality of adipose tissue (AT) play a more important role in manifestation of CM risk than quantity of AT alone. Detrimental health behaviours, such as low-quality diet and low levels of physical activity seem to be important contributors to this. Further studies can provide vital insights into the links between diet, location-specific adipose tissue, CM risk factors and health-related behaviours. Therefore this 8-weeks randomised pilot study will investigate the impact of either following a low-carbohydrate, high-fat diet versus following a high-carbohydrates, moderate-fat diet (UK dietary guidelines) on cardiometabolic risk markers and associated behaviours in a normal-weight and overweight adult population aged 19 - 64 at potential risk of CMD.

Official Title
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CALIBER (Carbohydrates, Lipids and Biomarkers of Traditional and Emerging Cardiometabolic Risk Factors) Phase 1: A Pilot Study in Normal-weight and Overweight Adults.

Conditions
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Cardiometabolic Risk

Intervention / Treatment
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* Other: Low-carbohydrate, high-fat
* Other: High-carbohydrate, moderate-fat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria cohort 1: BMI 18.5 - 29.9kg/m2 Aged 19 - 64 White-Caucasian Score of ≥4 from a combination of risk markers, including Fasting glucose concentration >5.5mmol/L = 3 points Waist >102cm or 40 inches = 2 points (males) Waist >94 cm or 37 inches = 1 point (males) Waist >88cm or 34inches = 2 points (females) Waist >80 cm or 31 inches = 1 point (females) Systolic blood pressure>130mmHg = 1 point Diastolic BP >85mmHg = 1 point HDL cholesterol concentration <1.0mmol/L = 2 points Serum triglyceride concentration >1.3mmol/L = 1 point. Exclusion Criteria cohort 1: Smoker Vegetarian or vegan Suffering from food allergies or intolerances Drinking alcohol above recommended UK government guidelines Previous diagnosis of CM disease Taking lipid-lowering medication Taking blood pressure-lowering medication Taking blood glucose-lowering medication Taking dietary supplements Suffering from an eating disorder Current or previous renal impairment Inclusion Criteria cohort 2: BMI 18.5 - 29.9kg/m2 Aged 19 - 64 White-Caucasian Exclusion Criteria cohort 2: Smoker Vegetarian or vegan Suffering from food allergies or intolerances Drinking alcohol above recommended UK government guidelines Previous diagnosis of CM disease Taking lipid-lowering medication Taking blood pressure-lowering medication Taking blood glucose-lowering medication Taking dietary supplements Suffering from an eating disorder Current or previous renal impairment

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-carbohydrate, high-fat<br>Participants adhering to low-carbohydrate, high-fat diet for 8 weeks. | Other: Low-carbohydrate, high-fat<br>* Participants following low-carbohydrate, high-fat diet for 8 weeks.<br>* Other names: CALIBER LCHF;|
| Experimental: High-carbohydrate, moderate fat<br>Participants following high-carbohydrate, moderate-fat diet for 8 weeks. | Other: High-carbohydrate, moderate-fat<br>* Participants following high-carbohydrate, moderate-fat diet (UK dietary guidelines) for 8 weeks.<br>* Other names: CALIBER HCMF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum lipid profile | Total cholesterol, HDL-C, LDL-C, non-HDL cholesterol, small-dense LDL-C and triglycerides measured in mmol/L | 8 weeks | 
| Blood glucose | Measured in mmol/L | 8 weeks | 
| Systolic and diastolic blood pressure | Measured in mmHg | 8 weeks | 
| Inflammatory markers, such as CRP | Measured in mg/L | 8 weeks | 
| Adiponectin | Measured in μg/mL | 8 weeks | 
| Fibroblast growth factor 21 (FGF21). | Measured in pg/mL | 8 weeks | 
| Tumor necrosis factor alpha and Interleukin 6 | Measured in μg/mL | 8 weeks | 
| Body composition - Bioelectrical impedance | Lean mass, fat mass and adipose tissue location and distribution | 8 weeks | 
| Body composition - Anthropometrics | Waist, hip, neck, thigh and calf circumference measured in cm | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical traditional and emerging markers of dietary intake | Fibroblast growth factor 21 and serum metabolites | 8 weeks | 
| Food cravings | Measured via self-reported questionnaire | 8 weeks | 
| Satiety | Assessed via serum leptin levels (ng/mL) | 8 weeks | 
| Cognition | Assessed via self-reported questionnaire | 8 weeks | 
| Impact on physical activity patterns | Assessed via accelerometry | 8 weeks | 
| Adherence to assigned diet | Measured via 4-day food diaries | 8 weeks | 
| Adherence to dietary guidelines | Measured via diet quality score assessment | 8 weeks | 
| Adherence to low-carbohydrate diet | Measured via blood ketones (mmol/L) | 8 weeks | 
| Adherence to fibre recommendations | Measured via structured questionnaires | 8 weeks | 
| Adherence to taking dietary supplement for low-carbohydrate, high-fat group | Measured via counting of number of multi-vitamin and mineral supplements consumed | 8 weeks | 
| Experience with either low-carbohydrate, high-fat or high-carbohydrate, moderate-fat diet | Assessed via semi-structured interview | 8 weeks |