Intranasal Insulin Treatment for Weight Management During Smoking Cessation

描述（由申请人提供）：戒烟后体重增加与吸烟复发的风险增加以及糖尿病的发展有关。到目前为止，还没有针对戒烟引起的体重增加的临床治疗方法。本项目旨在测试鼻内胰岛素治疗在控制食物摄入行为和代谢方面的功效。到目前为止，鼻内胰岛素治疗已经显示出特殊的安全性，初步数据表明它对体重相关参数有好处。鼻内给药可将胰岛素直接输送到中枢神经系统，没有明显的外周吸收，不会引起低血糖事件。鼻内胰岛素可以减少吃零食，同时减少游离脂肪酸的循环，而游离脂肪酸是导致糖尿病的主要代谢物。这是一项II期人体实验研究，其特定目标是为戒烟期间鼻内胰岛素治疗的更大规模III期试验提供疗效数据。本研究的受试者将参加两个阶段，他们将接受鼻内胰岛素和安慰剂。吃完早餐后，对他们的循环游离脂肪酸进行评估。我们假设鼻内胰岛素组与安慰剂组相比游离脂肪酸含量更低。午餐后两个半小时，受试者将参加模拟味觉测试。他们会被告知，测试的目的是对三种不同的菜肴的适口性进行评分。评分结束后，受试者将被告知剩余的饼干将被丢弃，他们可以随意吃多少。我们假设，在治疗（鼻内胰岛素）条件下，饼干的消耗量将低于安慰剂条件。该项目的里程碑包括证明鼻内胰岛素在尼古丁戒断期间对饱腹感和代谢谱的益处。

DESCRIPTION (provided by applicant): Weight gain following smoking cessation has been associated with increased risk of relapse to smoking as well as development of diabetes. To date, there are no clinical treatments that target weight gain caused by smoking cessation. This project proposes to test efficacy of intranasal insulin treatment in controlling behavioral and metabolic aspects of food intake. Thus far, intranasal insulin treatment has demonstrated an exceptional safety profile, and preliminary data indicate that it has benefits on weight-related parameters. Intranasal administration delivers insulin directly to the Central Nervous System, without a significant peripheral absorption that would cause hypoglycemic events. Intranasal insulin reduces snacking as well as circulating free fatty acids - metabolites that significantly contribute to the development of diabetes. This is a Phase II, human experimental study with a specific objective to provide efficacy data for a larger Phase III trial of intranasal insulin treatment during smoking cessation. Subjects in this study will participate in two sessions in which they will receive intranasal insulin and placebo. After eating breakfast, their circulating free fatty acids will be assessed. We hypothesize lower free fatty acids in the intranasal insulin vs. placebo condition. Two and a half hours after lunch, subjects will participate in a mock taste test. They will be told that the objective is to rate palatability of three different kinds of cookes. Following the ratings, subjects will be told that the remainder of cookies will be discarded and that they are free to eat however much they would like. We hypothesize that the cookie consumption in the treatment (intranasal insulin) condition will be lower in comparison to the placebo condition. Milestones for this project include demonstrating intranasal insulin's benefit on satiety and metabolic profile during nicotine withdrawal.