Improving Insulin Sensitivity by Non-invasive Brain Stimulation- Feasibility Study
试验速览
- 阶段
- 不适用
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Caloric intake (kcal)
研究概览
简要总结
Efforts in curing and preventing obesity and type 2 diabetes (T2D) have been elusive thus far. One reason for that is the lack of understanding of the role of the brain in the development and treatment of the disease. Insulin action in the brain is appreciated to play a vital role in the pathophysiology of T2D, influencing eating behavior, cognition and peripheral metabolism. Whether brain insulin resistance is a cause or consequence of prediabetes is not yet fully understood. Hence, in this project the investigators want to develop a novel tool to treat and prevent type 2 diabetes and to delineate brain mechanisms of insulin resistance in humans. For this purpose, transcranial direct current stimulation (tDCS) will be implemented, which is a powerful tool to stimulate brain networks. In recent studies, it was shown that the hypothalamus is part of a brain network including higher cognitive regions that is particularly vulnerable to insulin resistance. Furthermore, the central insulin response in this network predicted food craving and hunger. The investigators hypothesize that stimulating the hypothalamus-cognitive network will enhance insulin sensitivity and reduce food intake, food craving and hunger. Furthermore, the project will provide the unique opportunity to investigate novel mechanisms of insulin resistance in participants who have been extensively metabolically characterized.
详细描述
Objectives The overarching aim of the study is to stimulate the hypothalamus-cognitive brain network to improve insulin sensitivity and eating behavior.
Specific Objectives- Feasibility study:
- Implement resting-state functional magnetic resonance imaging to identify individual medial and lateral hypothalamic cognitive functional networks.
- Evaluate and test different non-invasive brain stimulation paradigms by tDCS to stimulate lateral and medial hypothalamus cognitive network on eating behavior and metabolism.
20 participants with overweight and obesity will receive five different tDCS stimulation protocols on five separate days (separated by one week) in a single-blind cluster-randomized order to reduce sequence effects. Optimal stimulation sites are assessed of the lateral and medial hypothalamus-cognitive network based on a modelling approach. Since this is the first study to stimulate the hypothalamus-cognitive network, excitatory as well as inhibitory stimulation is used. To reduce the number of conditions, participant are randomized based on the three main conditions: sham stimulation, anodal and cathodal stimulation. Medial hypothalamus-cognitive network versus lateral hypothalamus-cognitive network stimulation are pseudo-randomised.
Participants will come in the morning, after an overnight fast, to receive a 20 min non-invasive brain stimulation, using tDCS. During the stimulation, participants will perform a stop-signal task on an tablet.
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
- 20 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index (BMI) between 25.5 and 35 kg/m2
- •Age between 20 to 60 years of age
- •Criteria for prediabetes:
- •Fasting plasma glucose (PG) 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (impaired fasting glucose) OR 2-h PG during 75-g oral glucose tolerance test 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (impaired glucose tolerance) OR HbA1c 5.7-6.4% (39-47 mmol/mol)
排除标准
- •Insufficient knowledge of the German language
- •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
- •Previous bariatric surgery
- •Acute infection within the last 4 weeks
- •Hemoglobin values less than 12g/dl for women, less than 14 g/dl for men
- •Current participation in a lifestyle intervention study or a pharmaceutical study
- •Contradictions to a MRI measurement (e.g. metal implants)
研究组 & 干预措施
Anodal tDCS
Anodal tDCS of the lateral hypothalamus-cognitive or medial hypothalamus-cognitive network (2 conditions)
干预措施: anodal transcranial direct current stimulation (Device)
Cathodal tDCS
Cathodal tDCS of the lateral hypothalamus-cognitive or medial hypothalamus-cognitive network (2 conditions)
干预措施: cathodal transcranial direct current stimulation (Device)
Sham stimulation
Single blind sham stimulation (ramp-up ramp-down stimulation will be applied for 30 seconds in order to simulate the active condition without any further continuous administration of current)
干预措施: transcranial direct current stimulation (Device)
结局指标
主要结局
Caloric intake (kcal)
时间窗: 1 hour after tDCS
The investigators will assess free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented.
Change in subjective feeling of hunger and food craving
时间窗: 5 minutes before tDCS, 10 min after tDCS and 10 min after breakfast
On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using a questionnaire.
次要结局
- Food choice(10 minutes task after rating of food stimuli)
- Response inhibition(20 minutes during tDCS)
- Tastiness and healthiness rating of food stimuli(10 minutes task after breakfast)