Assessment of Mass Balance of Orally Administered [14C] (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one in Healthy Volunteers Using a Microtracer Approach
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- 14C (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one mass balance
研究概览
简要总结
Worldwide almost 40% of the adult population is overweight (including >10% obese), and more than 350 million children (up to the age of 19) are overweight. Overweight and obesity are significant problems and important risk factors for several lifestyle-related diseases, such as cardiovascular disease, certain cancers, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). Excessive consumption of glucose/sucrose is a major contributor to overweight and obesity. Alternative, low-calorie sweeteners could reduce daily energy intake and thus slow down the development of these conditions and related diseases. (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one is a sweetener that may be suitable for use as a sugar substitute; it is only partially digested in the small intestine and as a result has a lower energy density than more traditional sweeteners such as sucrose. However, it is not yet known to what extent (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one is used in the body and then excreted.
The aim of this study is to measure the metabolic utilization (the 'mass balance') of a single dose of 14C-labelled (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one and AMS technology. Based on clinical data of excretion (urine and faeces) and CO2 production (expired air), the mass balance can be derived. These generated results will be used to map the metabolic pathways (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one undergoes during the digestion process. In addition, it will provide insight into the use of AMS technology to investigate the relationship between diet and health.
详细描述
Objective
To determine the mass balance of (3S,4S,5R)-1,3,4,5,6-Pentahydroxy-hexan-2-one (low GI sweetener) in healthy volunteers.
Study design: Single centre, open-label, non-randomised, single oral administration study Study population: 8 healthy males and females (18-65 y, BMI 18.5-25 kg·m-2) Intervention: Orally ingestion of 14C-labelled (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one, followed by a 72-hour test period during which all urine and faeces will be collected, as well as repeated sampling of blood and expired air, as well as indirect calorimetry measurements.
Main study parameters/endpoints: Mass balance of (3S,4S,5R)-1,3,4,5,6-Pentahydroxy-hexan-2-one following 14C-(3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one ingestion. Secondary endpoints: content of 14C-labelled metabolites in carbohydrate metabolism pathways, routes of elimination of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one. Ventilated hood measurements will be used as proof of concept to assess caloric value of carbohydrates.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Insertion of the catheters in a vein is comparable to a normal blood draw and the only risk is a small local hematoma. (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one ingestion might lead to gastro-intestinal discomfort. During the adaptation period participants will consume food-grade (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one, which is safe for human consumption.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males and females using contraception during and for 3 months after the study, aged from 18-65 years at the time of signing the informed consent
- •18.5<BMI<25kg.m2
- •Willing and able to communicate and participate in the whole study, including consumption of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one and meals offered during study conduct
- •Regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)
- •Usually eat 3 meals per day (i.e. breakfast, lunch and dinner)
排除标准
- •Any diagnosed metabolic Impairment (e.g. Type 1 or 2 diabetes)
- •Any diagnosed cardiovascular disease
- •Hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastro-intestinal disease, immunodeficiency, endocrine, neurological or psychiatric disorders
- •Any diagnosed respiratory disease, such as COPD or asthma
- •Any previous motor disorders or disorders in muscle and/or lipid metabolism
- •Known severe kidney problems
- •Presence of an ulcer in the stomach or gut and/or strong history of indigestion
- •Recent or chronic history of diarrhoea
- •Known anaemia
- •A personal or family history of thrombosis (clots), epilepsy, seizures, or schizophrenia.
- •Regular use of dietary supplements (>3 times per week)
- •Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices)
- •History of any drug or alcohol abuse in the past two years
- •Claustrophobia
- •On a weight loss diet (including intermittent fasting) or following a high calorific/high protein diet in order to gain weight
- •Functional constipation
- •Any known food allergies or intolerances to the 14 major food allergens (celery, cereals containing gluten, crustaceans, eggs, fish, lupin, milk, molluscs, mustard, tree nuts, peanuts, sesame seeds, soybeans, sulphur dioxide and sulphites) or history of a malabsorption syndrome including coeliac disease
- •Regular gastrointestinal complaints including abdominal pain, stomach upsets and borborygmi or known or suspected irritable bowel syndrome
- •Currently taking part in other scientific research
- •Received a product with 14C in the past 12 months
- •Pregnant or breastfeeding
- •Smoking or having used nicotine-containing products in the 6 months prior to the study.
- •Taken antibiotics within the 60 days prior to the adaptation period.
- •Currently involved in a structured progressive resistance training programme (>3 times per week)
- •Sedentary lifestyle as assessed using the International Physical Activity Questionnaire [IPAQ].
- •Employed or undertaking a thesis or internship at the department of Human and Animal Physiology or TNO (department of Metabolic Health Research)
- •Unable to give consent
结局指标
主要结局
14C (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one mass balance
时间窗: day 0-3 test period
Mass balance recovery after a single oral dose of 14C (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one
次要结局
- 14C (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one elimination routes(day 0-3 test period)
- Metabolite profiling of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one metabolites(day 0-3 test period)
- Quantification of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one metabolites(day 0-3 test period)
- Structural identification of (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one metabolites(day 0-3 test period)
- (3S,4S,5R)-1,3,4,5,6-pentahydroxy-hexan-2-one pathway activity(day 0-3 test period)
- Resting energy expenditure(day 0-3 test period)
- Rate of whole-body substrate oxidation(day 0-3 test period)
研究者
Marlou Dirks
Assistant Professor
Wageningen University