Effects of Intranasal Insulin Administration on Tissue Specific Insulin Sensitivity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Skeletal muscle glucose uptake
研究概览
简要总结
Recent research has suggested that intranasally administered insulin can reach the brain quickly without passing through circulation and evoke increased insulin sensitivity and tissue glucose consumption during insulin stimulation (low-dose hyperinsulinemic, euglycemic clamp). It is still not known what mechanism causes these changes or what tissues are involved in this.
In this study, the changes in tissue-specific insulin sensitivity and glucose uptake will be investigated by using glucose-analogue radiotracer ([18F]-fluorodeoxyglucose) with positron emission tomography (PET) imaging during insulin stimulation. Ten healthy males are studied, each receiving nasal sprays containing insulin or placebo in a randomized order on two separate days. After spray administration, glucose uptake in skeletal muscle, liver, subcutaneous and visceral adipose tissue, myocardium, intestines, brown adipose tissue and brain assessed by PET imaging and glucose uptake in these tissues is analyzed. Endogenous glucose production is calculated facilitating the measurements glucose and radiotracer uptake in tissues and tracer loss into urine.
As skeletal muscle consumes most of the glucose available, it is likely that administration of insulin sprays will result in an increased uptake in this tissue. Some increase in glucose uptake might also be seen in other tissue types after insulin spray versus placebo spray administration.
详细描述
The objective of this study is to investigate the effects of intranasally administered insulin versus placebo on tissue specific glucose uptake of the key metabolic organs as well as on endogenous glucose production.
SAMPLE SIZE:
A total of ten (n=10) healthy males are planned to be included, and the study is conducted with a cross-over design with each subject being investigated twice, once using intranasal insulin and once using intranasal placebo in single-blinded randomized order.
SCREENING VISIT/ELIGIBILITY:
Main inclusion and exclusion criteria will be evaluated at a screening visit. This visit will include a frequently-sampled 75 g oral glucose tolerance test as well as anthropometric measurements and clinical examination.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •BMI 18,5-25 kg/m2
- •Fasting plasma glucose less than 6.1 mmol/l
- •Normal 2-hour oral glucose tolerance test (OGTT)
排除标准
- •Any chronic disease or medication that could affect glucose metabolism
- •History of anorexia nervosa or bulimia
- •Smoking of tobacco, taking of snuffs, or use of narcotics
- •Abusive use of alcohol
- •Any other condition that in the opinion of the investigator could create a hazard to the subject safety, endanger the study procedures or interfere with the interpretation of study results
研究组 & 干预措施
Insulin nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain fast-acting human insulin Actrapid (Novo Nordisk A/S, Bagsvaerd, Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd, Denmark) over 15 minutes.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: Actrapid (Drug)
Insulin nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain fast-acting human insulin Actrapid (Novo Nordisk A/S, Bagsvaerd, Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd, Denmark) over 15 minutes.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: [18F]-FDG PET-CT (Radiation)
Insulin nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain fast-acting human insulin Actrapid (Novo Nordisk A/S, Bagsvaerd, Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd, Denmark) over 15 minutes.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: Hyperinsulinemic euglycemic clamp (Drug)
Placebo nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain Insulin Diluting Medium for Novorapid and Levemir (Novo Nordisk A/S, Bagsvaerd,Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd,Denmark) over 15 min.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: Placebo (Drug)
Placebo nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain Insulin Diluting Medium for Novorapid and Levemir (Novo Nordisk A/S, Bagsvaerd,Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd,Denmark) over 15 min.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: [18F]-FDG PET-CT (Radiation)
Placebo nasal spray
Subjects administer 2 intranasal sprays into each nostril every minute for 4 minutes, a total of 16 sprays. Sprays contain Insulin Diluting Medium for Novorapid and Levemir (Novo Nordisk A/S, Bagsvaerd,Denmark). The glass spray flasks are produced by AeroPump GmBH, Germany and give 0,1 ml of fluid per spray. To account for the small amount of insulin absorbed into circulation after the insulin nasal sprays, on the placebo day subjects will be administered 2.5 mU/kg of additional intravenous insulin (Actrapid, Novo Nordisk A/S, Bagsvaerd,Denmark) over 15 min.
30 min before spray administration a hyperinsulinemic euglycemic clamp will be started and continued for 170 minutes. 40 min after spray administration [18F]-FDG PET-CT scan lasting 100 min is started.
干预措施: Hyperinsulinemic euglycemic clamp (Drug)
结局指标
主要结局
Skeletal muscle glucose uptake
时间窗: Data is collected during 100 min PET scan started 40 min after spray administration.
Change in skeletal muscle insulin stimulated glucose uptake (μmol/min/kg) after insulin versus placebo nasal spray administration.
次要结局
- Endogenous glucose production(Data is collected during 100 min PET scan started 40 min after spray administration.)
- Liver glucose uptake(Data is collected during 100 min PET scan started 40 min after spray administration.)