Impact of the Incretin System on Brain Insulin Sensitivity in Humans with Normal Weight, Overweight and Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Cerebral response after insulin compared to placebo nasal spray
研究概览
简要总结
The overarching goal of the current study is to investigate the effect of GLP-1 on brain insulin responsiveness in a randomized, single-blinded, within subject cross-over study design. To this end, investigators will compare the effect of the administration of semaglutide versus placebo, followed by an fMRI with administration of intranasal insulin or placebo.
详细描述
Investigate the effect of the GLP1 receptor agonist (i.e. 0.25 mg semaglutide) vs. placebo on the brain using functional magnetic resonance imaging (fMRI) in combination with 160IU intranasal insulin vs. placebo administration in healthy male and female participants of normal-weight and overweight/obesity. Participants will furthermore undergo tasks that assess cognitive functions and eating behavior. Brain insulin responsiveness (primary outcome) is defined as the cerebral response to intranasal insulin compared to placebo by means of cerebral blood flow and resting-state BOLD measurements. Secondary outcomes include diffusion weighted imaging, neural food cue reactivity, cognitive functions and metabolic predictors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- 是
入选标准
- •BMI between 18.5 and 24.9 kg/m2; and between 27.5 kg/m2 and 40 kg/m2
- •Written consent to participate in the study
- •Written consent to be informed about incidental findings
排除标准
- •Type 1 or type 2 diabetes, LADA, MODY, or cardiovascular diseases such as chronic heart failure, myocardial infarction, status post stroke
- •BMI < 18.5 or > 40 kg/m2
- •Persons who cannot legally give consent
- •Pregnancy or lactation
- •History of severe mental or somatic disorders including neurological diseases (incl. epileptic seizures)
- •Taking psychotropic drugs
- •Chronic diseases or medication that influence glucose metabolism
- •Regular use of analgesic drugs
- •Previous bariatric surgery
- •Known allergy against one or more of the used agents
- •Acute infection and/or antibiotic treatment within the last 4 weeks
- •Hemoglobin values less than 10.5 g/dl for women, less than 11.5 g/dl for men
- •Other diseases that in the opinion of the investigator may jeopardize the success of the study or indicate a risk to the volunteer
- •Participation in a lifestyle intervention study or a pharmaceutical study within the last 30 days
- •Metal implants which cannot be removed as pacemakers, artificial heart valve, electrical devices as insulin pumps, large tattoos, retainer over more than 4 teeth, contraceptive coil, implanted magnetic metal parts as screws or plates after a surgery
- •Persons with claustrophobia
- •Persons with tinnitus
- •Weight loss or gain of >5% in the last 3 months
- •Pancreatic diseases
- •History or family history of multiple endocrine neoplasia (MEN2) or medullary thyroid cancer
- •History of malignant thyroid disease
- •History of malignant disease in the past 5 years
- •Surgery in the last three months
- •Chronic tobacco use of more than 10 cigarettes/day
- •Women who do not consent to refrain from breastfeeding until 2 months after the end of the study
- •Women of childbearing age who do not consent to use safe method of contraception from 28 days before until 2 months after the end of the study or refrain from heterosexual intercourse during this time
- •Women of childbearing age who do not consent to take a pregnancy test
结局指标
主要结局
Cerebral response after insulin compared to placebo nasal spray
时间窗: 24 hours after semaglutide or placebo administration
Resting-state cerebral blood flow and BOLD-fMRI response from before to 30 min after nasal spray administration
次要结局
- Heart rate variability (HRV)(24 hours after semaglutide or placebo administration)
- Neural food-cue reactivity after insulin compared to placebo nasal spray(24 hours after semaglutide or placebo administration)
- Diffusion-weighted imaging (DWI)(24 hours after semaglutide or placebo administration)
- Change in subjective feeling of hunger and food craving(24 hours after semaglutide or placebo administration)
- Change in mood(24 hours after semaglutide or placebo administration)
- Performance during cognitive tests(24 hours after semaglutide or placebo administration)