Why do Some Patients Respond Better Than Others to Bariatric Surgery?
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Gut hormone secretion study: Peak plasma level of gut hormones after meal ingestion
研究概览
简要总结
Obesity and type 2 diabetes are major causes of illness and premature death worldwide and their incidence is increasing rapidly. Bariatric surgery is considered as the "gold-standard" surgical treatment for both conditions.
However, not all patients do equally well after surgery and indeed the weight loss experienced by patients undergoing bariatric surgery can vary. As such when patients are seen after bariatric surgery in clinic they fall in one of the following two categories:
- Good responders: this is the majority of patients who lose the expected amount of weight based on the published studies.
- Poor responders: this is a small group of patients who either lose less than the expected amount of weight after bariatric surgery or lose the expected amounts of weight early after surgery but then regain a substantial proportion of the weight they have lost.
The so-called "poor responders" are exposed to all the risks of the operation and do not benefit from the weight loss as much as good responders.
This study would therefore like to investigate the physiological factors that distinguish poor from good responders before, and after bariatric surgery. The study team hypothesizes that compared to good responders, poor responders exhibit:
- a smaller degree of fullness sensation after a meal,
- a lower energy expenditure after a meal, and
- genetic changes (single nucleotide polymorphisms) that predispose the poor responder to development of obesity.
In addition, the study team hypothesizes that poor responders exhibit:
- lower gut hormone secretion after a meal and
- are less sensitive to the physiological action of gut hormones compared to good responders and that this difference in gut hormone secretion and response to gut hormones prior to bariatric surgery can be helpful to predict response to bariatric surgery.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 -70 years.
- •Male or female.
- •Previous bariatric surgery for obesity and/or diabetes (studies 1 and 2).
- •≥1 year interval after bariatric surgery (studies 1 and 2).
- •Awaiting bariatric surgery at the Imperial Weight Centre (study 3)
- •Able to give informed consent.
排除标准
- •History of any medical, psychological or other condition, or use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer.
- •Without access at home to a telephone or other factor likely to interfere with ability to participate reliably in the study.
- •Pregnancy or breastfeeding.
- •Unable to maintain adequate contraception for the duration of the study and for one month afterwards.
- •History of hypersensitivity to any of the components of the subcutaneous infusions.
- •Donated blood during the preceding 3 months or intention to do so before the end of the study.
- •Any other co-morbidity that would compromise the validity of the study or the safety of the participant such as heart failure or clinically apparent cardiovascular disease.
- •Anatomical or endocrinological pathology causing poor weight loss or weight regain
- •Uncontrolled hypertension (systolic blood pressure of 160 mmHg or above and/or diastolic blood pressure of 100 mmHg or above)
- •Participation in a research study within the last two months.
- •Unable to speak English (this is relevant to answering the psychological questionnaires)
研究组 & 干预措施
Gut hormone secretion study
This will be a retrospective study of participants who have undergone bariatric surgery. On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests:
- Body weight and bioelectrical impedance analysis
- Mixed Meal Tolerance Test. This will be analysed for metabolites including gut hormones, insulin, glucose, bile acids and their sub-fractions, fibroblast-growth factors, lipids and immune profiles.
- Resting Energy Expenditure and Diet Induced Thermogenesis assessed via Indirect Calorimetry
- Metabolomic and Metagenomic Assessment
Gut hormone sensitivity study
This will be a single blinded study with participants attending three visits. Their first visit will act as an acclimatisation visit and participants will be infused subcutaneously with a triple gut hormone infusion (GLP-1, PYY and OXM). This will not only allow us to acclimatise the study volunteer to the study visits, but also allow us to test for subject tolerability of the gut hormones. Occasionally some volunteers are more sensitive to the gut hormone infusion and the doses needs to be titrated down. The doses used will be established doses of the gut hormones infused previously and which have been shown to be safe and tolerated, and to reduce appetite (In house data).
干预措施: Gut hormones (Other)
Prospective assessment of gut hormone response pre and post-surgery
This will be a prospective study assessing the gut hormone response pre and post bariatric surgery.
On the day of the visit participants will undergo comprehensive physiological profiling which will include the following tests:
- Body weight and bioelectrical impedance analysis
- Mixed Meal Tolerance Test. This will be analysed for metabolites including gut hormones, insulin, glucose, bile acids and their sub-fractions, fibroblast-growth factors, lipids and immune profiles.
- Resting Energy Expenditure and Diet Induced Thermogenesis assessed via Indirect Calorimetry
- Metabolomic and Metagenomic Assessment
结局指标
主要结局
Gut hormone secretion study: Peak plasma level of gut hormones after meal ingestion
时间窗: During one study visit (Mixed Meal Test), at least 1 year post-surgery.
A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.
Prospective assessment of gut hormone response pre and post-surgery: Change in Peak plasma level of gut hormones after meal ingestion.
时间窗: During two study visits (Mixed Meal Test), one before and one 1 year after surgery.
A standardized mixed-meal tolerance test. Blood samples will be taken at intervals over four hours. These will be analysed for gut hormones.
Gut hormone sensitivity study: Change in Food intake following gut hormone infusion compared to placebo.
时间窗: During three study visits (gut hormone infusion visits), at least 1 year post-surgery.
Ad libitum meal test. A meal will be served to participants and they will be allowed 20 minutes to eat until they feel comfortably full. Food intake will be measured at the end of the meal.
次要结局
- Change in Diet Induced Thermogenesis(Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).)
- Change in Genetic factors(Change between two visits: Before and 1 year after bariatric surgery.)
- Change in Resting Energy Expenditure(Change between two visits: before and 1 year after bariatric surgery (Prospective assessment of gut hormone response pre and post-surgery).)