The Impact of Pramlintide on Top of Semaglutide in Obese People With Prediabetes
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change in kilocalorie (kCal) consumption at ad libitum meal test, from baseline, to after 26 weeks of semaglutide of which the last two weeks is with the addition of either pramlintide or placebo
研究概览
简要总结
The two main aims of this clinical study is;
- To investigate if the results from a series of physiological tests and questionnaires prior to treatment, can be used to predict the treatment response to obesity medication
- To investigate the effect of combining semaglutide and pramlintide on various aspects of appetite, food preference and eating habits.
The study is planed as a 26 week, double blinded, randomized, placebo controlled trial. The goal is to include N=40. They will all receive weekly semaglutide injections. After 24 weeks they will be randomized to receive either an amylin analog (pramlintide) or placebo as a continuous infusion for two weeks, in addition to weekly semaglutide.
The results from this study will contribute to identifying possible predictors of treatment response, enabling optimal individualized medical weight loss treatment. As well as providing knowledge on the complex interplay between incretin hormones and their effects on appetite and eating habits.
详细描述
Obesity is a major global health challenge and the prevalence of obesity is increasing. Presence of obesity increases the risk of several diseases, physical limitations and an increased mortality. When weightloss is wanted in order to avoid or treat some of these diseases, medical weight loss treatment is one of the options. Among these modified gut hormones, such as Glucagon Like Peptide -1 Receptor agonists (GLP-1RA). However, the individual response to GLP-1RA treatments varies considerably. Currently the best predictor of total weight loss is achieved weight loss after three months of treatment. With more pharmaceutical options to come, a trial and error approach is not appropriate. There is a need to identify possible pre-treatment predictors to treatment response.
This is one of the project's main aims. By being able to predict the treatment response, one can tailor the obesity treatment to the individual improving the treatment outcome.
Amylin is co-secreted with insulin from the pancreas in response to meals. It is found to have many similar effects in the body as GLP-1. However their combination, especially on appetite, food preferences and eating pattern is sparsely investigated. This is the other main aim of the project.
This clinical study will be a 26 week, randomized, double-blinded, placebo-controlled trial. Forty overweight (BMI ≥30kg/m2) individuals with pre-diabetes (HbA1c 39-47 mmol/mol) will all receive once-weekly semaglutide for 26 weeks. Semaglutide will be given in escalating doses aiming to reach the maximal dose of 2.4 mg (maximum dosage approved for treatment of overweight), but accepting lower maximal tolerable dosage.
After 24 weeks of treatment, they will be stratified according to their weight loss (<15% or ≧15%) and based on this stratification, block randomized 1:1 to receive either pramlintide or placebo(normal isotonic 0.9% saline solution) in addition to weekly semaglutide. Pramlintide will be continuously infused, starting at a dosage of 7,5 mcg/hour for three days, and if tolerated, the dosage will be increased to 15 mcg/hour for the remaining eleven days. Previous studies have found measurable changes in appetite after a single dosage of pramlintide, and measurable weight loss after two weeks of treatment. For the continuous infusion a commercially available insulin pump will be used.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- 是
入选标准
- •BMI ≧ 30kg/m2
- •HbA1c 39-47 mmol/mol (pre-diabetes)
- •Male or female
- •Aged >18 years of age and <70 years
- •Negative pregnancy test, and willing to use contraceptives during the study period
排除标准
- •Presence of diabetes with or without treatment
- •Current or recent (<6 months) treatment with GLP1 RA's
- •Previous gastrointestinal surgery that might affect gastric emptying, nutritional absorption and postprandial GI peptide production
- •History of acute or chronic pancreatitis
- •Chronic kidney disease
- •Use of any antipsychotic drugs
- •Use of any antiresorptive or bone-anabolic drugs or fractures within < 6 months
- •Use of systemic oral glucocorticoids within < 6 months
- •Newly (< 3 months) initiated hormonal contraceptive or other hormone therapy
- •Recent (<3 months) weight loss ≧ 1% of body weight
- •Presence of Binge eating disorder
研究组 & 干预措施
Semaglutide and placebo
All subjects will receive weekly semaglutide inj. for 26 weeks. After 24 weeks of treatment, this group will be randomized to receive placebo, in addition to semaglutide for the last two weeks of the study.
干预措施: Semaglutide Pen Injector (Drug)
Semaglutide and placebo
All subjects will receive weekly semaglutide inj. for 26 weeks. After 24 weeks of treatment, this group will be randomized to receive placebo, in addition to semaglutide for the last two weeks of the study.
干预措施: Sodium Chloride 0.9% Inj (Drug)
Semaglutide and pramlintide
All subjects will receive weekly semaglutide inj. for 26 weeks. After 24 weeks of treatment, this group will be randomized to receive pramlintide, in addition to semaglutide for the last two weeks of the study.
干预措施: Pramlintide Acetate 1 MG/ML (Drug)
Semaglutide and pramlintide
All subjects will receive weekly semaglutide inj. for 26 weeks. After 24 weeks of treatment, this group will be randomized to receive pramlintide, in addition to semaglutide for the last two weeks of the study.
干预措施: Semaglutide Pen Injector (Drug)
结局指标
主要结局
Change in kilocalorie (kCal) consumption at ad libitum meal test, from baseline, to after 26 weeks of semaglutide of which the last two weeks is with the addition of either pramlintide or placebo
时间窗: From baseline at the start of the study(week 0), to the end of the study after 26 weeks
次要结局
- Change in appetite and satiety sensations as measured by Visual Analog Scale (VAS) prior to and following the meal tests(From baseline(week 0) to after 24 weeks, and to the end of the study(week 26))
- Change in gastric emptying rate assessed by paracetamol (acetaminophen) test(From baseline (week 0) to end of study(week 26))
- Total weight loss(From baseline(week 0) to after 24 weeks, and to the end of the study(week 26))
- Difference in total weight loss between the subgroups (Obesity phenotypes)(From baseline (week 0) to end of study (week 26))