Protocol for a multicentre, parallel, randomised, controlled trial on the effect of sweeteners and sweetness enhancers on health, obesity and safety in overweight adults and children: the SWEET project.

The aim of this randomised controlled trial (RCT) is to investigate whether prolonged consumption of sweeteners and sweetness enhancers (S&SEs) within a healthy diet will improve weight loss maintenance and obesity-related risk factors and affect safety markers compared with sugar. SWEET (S&SEs: prolonged effects on health, obesity and safety) is a 1-year multicentre RCT including at least 330 adults with overweight (18-65 years, body mass index (BMI) >25 kg/m2) and 40 children (6-12 years, BMI-for-age >85th percentile). In an initial 2-month period, adults will consume a low-energy diet with the aim to achieve ≥5% weight loss. Children are advised to consume a generally healthy diet to maintain body weight, thus reducing their BMI-for-age z-score. In the following 10 months, participants will be randomised to follow a healthy ad libitum diet with or without S&SE products. Clinical investigations are scheduled at baseline, after 2, 6 and 12 months. The primary outcomes are body weight for efficacy and gut microbiota composition (in relation to metabolic health) for safety, both in adults. Secondary outcomes include anthropometry, risk markers for type-2 diabetes and cardiovascular diseases, questionnaires including, for example, food preferences, craving and appetite and tests for allergenicity. The trial protocol has been approved by the following national ethical committees; The research ethics committees of the capital region (Denmark), approval code: H-19040679, The medical ethics committee of the University Hospital Maastricht and Maastricht University (the Netherlands), approval code: NL70977.068.19/METC19-056s, Research Ethics Committee of the University of Navarra (Spain), approval code: 2019.146 mod1, Research Ethics Committee of Harokopio University (Greece), approval code: 1810/18-06-2019. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed scientific journals regardless of whether the findings are positive, negative or inconclusive. NCT04226911 (Clinicaltrials.gov).

Kjølbæk L ，Manios Y ，Blaak EE ，Martínez JA ，Feskens EJM ，Finlayson G ，Andersen SSH ，Reppas K ，Navas-Carretero S ，Adam TC ，Hodgkins CE ，Del Álamo M ，Lam T ，Moshoyiannis H ，Halford JCG ，Harrold JA ，Raben A ... -  《BMJ Open》

Acute and repeated impact of sweeteners and sweetness enhancers in solid and semi-solid foods on appetite: protocol for a multicentre, cross-over, RCT in people with overweight/obesity - the SWEET Project.

Intake of free sugars in European countries is high and attempts to reduce sugar intake have been mostly ineffective. Non-nutritive sweeteners and sweetness enhancers (S&SEs) can maintain sweet taste in the absence of energy, but little is known about the impact of acute and repeated consumption of S&SE in foods on appetite. This study aims to evaluate the effect of acute and repeated consumption of two individual S&SEs and two S&SE blends in semisolid and solid foods on appetite and related behavioural, metabolic and health outcomes. A work package of the SWEET Project; this study consists of five double-blind randomised cross-over trials which will be carried out at five sites across four European countries, aiming to have n=213. Five food matrices will be tested across three formulations (sucrose-sweetened control vs two reformulated products with S&SE blends and no added sugar). Participants (body mass index 25-35 kg/m2; aged 18-60 years) will consume each formulation for 14 days. The primary endpoint is composite appetite score (hunger, inverse of fullness, desire to eat and prospective food consumption) over a 3-hour postprandial incremental area under the curve during clinical investigation days on days 1 and 14. The trial has been approved by national ethical committees and will be conducted in accordance with the Declaration of Helsinki. Results will be published in international peer-reviewed open-access scientific journals. Research data from the trial will be deposited in an open-access online research data archive. NCT04633681.

Gibbons C ，O'Hara B ，O'Connor D ，Hardman C ，Wilton M ，Harrold JA ，Almiron-Roig E ，Navas-Carretero S ，Hodgkins CE ，Nazare JA ，Alligier M ，Martínez JA ，Scott C ，Kjølbæk L ，Normand M ，Rannou C ，Blaak EE ，Feskens E ，Moshoyiannis H ，Raben A ，Halford JCG ，Beaulieu K ，Finlayson G ... -  《BMJ Open》

Study protocol of the sweet tooth study, randomized controlled trial with partial food provision on the effect of low, regular and high dietary sweetness exposure on sweetness preferences in Dutch adults.

Čad EM ，Tang CS ，de Jong HBT ，Mars M ，Appleton KM ，de Graaf K ... -  《BMC PUBLIC HEALTH》

Protocol for a single-centre, parallel-group, randomised, controlled, superiority trial on the effects of time-restricted eating on body weight, behaviour and metabolism in individuals at high risk of type 2 diabetes: the REStricted Eating Time (RESET) st

The aim of this study is to investigate the effects of time-restricted eating (TRE) on change in body weight and describe changes in behaviour and metabolism in individuals at high risk of type 2 diabetes. The REStricted Eating Time (RESET) study is a randomised controlled parallel-group open-label trial. 100 women and men with (1) overweight (body mass index (BMI)≥25 kg/m2) and prediabetes (glycated haemoglobin 39-47 mmol/mol); or (2) obesity (BMI≥30 kg/m2) will be randomised to a control group (habitual living) or TRE (self-selected 10-hours eating window within the period from 06:00 to 20:00 in a 1:1 ratio. Testing is scheduled at baseline and after 6 weeks (mid-intervention), 3 months (post-intervention) and 6 months (follow-up). The primary outcome is change in body weight after 3 months of intervention. Secondary outcomes include changes in body composition; measures of glucose metabolism including glycaemic variability, hormones and metabolites; subjective and metabolic markers of appetite, food preferences and reward; dietary intake; physical activity, sleep, chronotype; gastric emptying, gastrointestinal transit time and motility; respiratory and glycolytic capacities; the plasma proteome and metabolome; blood pressure, resting heart rate and heart rate variability; and resting energy expenditure and substrate oxidation. Motivation and feasibility will be examined based on interviews at baseline and after 3 months. After the 3-month intervention, a 3-month follow-up period and subsequent testing are scheduled to assess maintenance and longer-term effects. The study has been approved by the Ethics Committee of the Capital Region of Denmark (H-18059188) and the Danish Data Protection Agency. The study will be conducted in accordance with the Declaration of Helsinki. Results from the study will address whether TRE is effective and feasible in improving health outcomes in individuals at risk of lifestyle-related diseases and can potentially inform the design of feasible health recommendations. NCT03854656.

Quist JS ，Jensen MM ，Clemmensen KKB ，Pedersen H ，Bjerre N ，Størling J ，Blond MB ，Wewer Albrechtsen NJ ，Holst JJ ，Torekov SS ，Vistisen D ，Jørgensen ME ，Panda S ，Brock C ，Finlayson G ，Færch K ... -  《-》

Effects of a carbohydrate-reduced high-protein diet delivered with meal kits to Danish people with type 2 diabetes: protocol for a 12-month randomised controlled trial.

The cornerstone in the management of type 2 diabetes (T2D) is lifestyle modification including a healthy diet, typically one in which carbohydrate provides 45%-60% of total energy intake (E%). Nevertheless, systematic reviews and meta-analyses of trials with low carbohydrate diets (which are increased in protein and/or fat) for T2D have found improved glycaemic control in the first months relative to comparator diets with higher carbohydrate content. Studies lasting ≥1 year are inconclusive, which could be due to decreased long-term dietary adherence. We hypothesise that glucometabolic benefits can be achieved following 12 months of carbohydrate-restricted dieting, by maximising dietary adherence through delivery of meal kits, containing fresh, high-quality ingredients for breakfast, dinner and snacks, combined with nutrition education and counselling. This protocol describes a 12-month investigator-initiated randomised controlled, open-label, superiority trial with two parallel groups that will examine the effect of a carbohydrate-reduced high-protein (CRHP) diet compared with a conventional diabetes (CD) diet on glucometabolic control (change in glycated haemoglobin being the primary outcome) in 100 individuals with T2D and body mass index (BMI) >25 kg/m2. Participants will be randomised 1:1 to receive either the CRHP or the CD diet (comprised 30/50 E% from carbohydrate, 30/17 E% from protein and 40/33 E% from fat, respectively) for 12 months delivered as meal kits, containing foods covering more than two-thirds of the participants' estimated daily energy requirements for weight maintenance. Adherence to the allocated diets will be reinforced by monthly sessions of nutrition education and counselling from registered clinical dietitians. The trial has been approved by the National Committee on Health Research Ethics of the Capital Region of Denmark. The trial will be conducted in accordance with the Declaration of Helsinki. Results will be submitted for publication in international peer-reviewed scientific journals. NCT05330247. The trial protocol was approved on 9 March 2022 (study number: H-21057605). The latest version of the protocol, described in this manuscript, was approved on 23 June 2023.

Kopp LHP ，Søgaard-Hansen CM ，Zachhau KM ，Bastkjær RM ，Andersen BV ，Budtz-Jørgensen E ，Byrne DV ，Chaaban N ，Holst JJ ，Klindt TB ，Magkos F ，Ozenne B ，Samkani A ，Skytte MJ ，Madsbad S ，Krarup T ，Thomsen MN ... -  《-》