Neuroimmune Mechanisms in Obesity
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Baseline [11C]PBR28 VT values
研究概览
简要总结
Aim 1: To measure levels of microglia using the radiotracer [11C]PBR28 and PET brain imaging in obese (n=50) vs. lean individuals (n=50). The investigators will recruit 100 subjects who will participate in a single [11C]PBR28 scan to measure levels of TSPO, a marker of microglia.
Aim 2: To determine differences in brain functional connectivity at rest and in response to a decision- making task in obese (n=50) vs. lean individuals (n=50) using fMRI imaging. The same subjects from Aim 1 will participate in a resting state functional magnetic resonance imaging (fMRI) followed by a decision making task during fMRI acquisition.
Aim 3: To assess whether acute elevation of lipid levels through intralipid infusion in lean, healthy individuals (n=20) will induce microglial activation. 20 lean individuals will be recruited to participate in a paradigm that includes a baseline [11C]PBR28 scan, an infusion of intralipid, and a second [11C]PBR28 scan approximately 4 hours post intralipid infusion. The investigators will attempt to utilize subjects from aim 1 in order to use their baseline scans for this paradigm.
Aim 4: To determine whether there are differences in levels of microglia between individuals with and without type 1 diabetes (n=20). 20 patients with diabetes (type 1 diabetes or type 2 diabetes)will be recruited to participate in a single [11C]PBR28 scan to compare to Aim 1 participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-55 years
- •Able to read and write English and provide voluntary informed consent
- •Physically and psychiatrically healthy by medical history, physical, psychiatric, neurological, EKG and laboratory examinations
- •For Aims 1-3: HbA1C < 5.7%
- •For Aim 4: HbA1C >6.5% and known diagnosis of T1DM or T2DM
排除标准
- •Abnormal labs including Creatinine>1.5mg/dL, Hematocrit < 35% for females and < 39% for males, ALT/AST >2.5X upper limit of normal, abnormal TSH
- •Known significant thyroid, hepatic, neurologic, psychiatric, cerebrovascular, or cardiovascular disease
- •>5% body weight change in last 6 months
- •Current or recent regular steroid use in last 6 months, illicit drug use that is deemed to interfere with results including problematic alcohol use as defined by NIAAA
- •Current regular use of psychotropic and/or potentially psychoactive prescription medications
- •Regular use of any vitamins/supplements that could affect lipids
- •Current regular use of non-steroidal anti-inflammatory medications, statins, or lipid lowering agents
- •Vaccination in the last month
- •Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)
- •For females, physical or laboratory (-HCG) evidence of pregnancy, seeking pregnancy, or lactating. A urine drug screen and pregnancy test will be performed at screening and prior to the imaging session. Subjects who screen positive will be excluded.
- •Note: If a subject tests positive for an illicit substance, the PI will determine if the substance would interfere with the results and may terminate participation if applicable. Results of the test would only be noted in the subjects de-identified chart to document the occurrence.
研究组 & 干预措施
Post-Intralipid Infusion [11C]PBR28 PET Scan
Subjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion
干预措施: Intralipid Infusion (Drug)
结局指标
主要结局
Baseline [11C]PBR28 VT values
时间窗: At baseline
\[11C\]PBR28 VT values in our primary regions of interest (PFC and hippocampus) from PET Scan. Linear mixed-effect models will be conducted to evaluate differences in \[11C\]PBR28 VT values between lean, healthy controls (n=40) and individuals with obesity (n=40), controlling for rs6971 genotype, age, and sex.
Post-Intralipid [11C]PBR28 VT values
时间窗: Approximately 3 Hours After Intralipid Infusion
\[11C\]PBR28 VT values in our primary regions of interest (PFC and hippocampus) from PET Scan. Linear mixed-effect models will be conducted to evaluate differences in \[11C\]PBR28 VT values between lean, healthy controls (n=40) and individuals with obesity (n=40), controlling for rs6971 genotype, age, and sex.
Baseline Functional Connectivity
时间窗: At baseline
ICD values will be obtained from primary a priori regions of interest (vmPFC and hippocampus) with PET Scan. Independent t-tests will be used to compare the ICD data between the study groups.
Post-Intralipid Functional Connectivity
时间窗: Approximately 3 Hours After Intralipid Infusion
ICD values will be obtained from primary a priori regions of interest (vmPFC and hippocampus) with PET Scan. Independent t-tests will be used to compare the ICD data between the study groups.
Baseline Microglial Activation
时间窗: At baseline
Regional \[11C\]PBR28 VT values from pre-lipid infusion PET Scan
Post-Intralipid Microglial Activation
时间窗: Approximately 3 Hours After Intralipid Infusion
Percent change in regional \[11C\]PBR28 VT values from pre-lipid infusion PET Scan to post-lipid infusion PET Scan will be calculated across brain regions. Increased microglial activation will be measured as a 20% or more increase in TSPO levels from scan 1 to scan 2
次要结局
- Baseline Visual Attention(At baseline)
- Post-Intralipid Infusion Visual Attention(Approximately 1 Hour After Intralipid Infusion)
- Baseline Visual Learning(At baseline)
- Post-Intralipid Infusion Visual Learning(Approximately 1 Hour After Intralipid Infusion)
- Baseline Verbal Memory(At baseline)
- Post-Intralipid Verbal Memory(Approximately 1 Hour After Intralipid Infusion)
- Baseline Executive Function(At baseline)
- Post-Intralipid Executive Function(Approximately 1 Hour After Intralipid Infusion)
- Baseline Visual-Motor Processing Speed(At baseline)
- Post-Intralipid Visual-Motor Processing Speed(Approximately 1 Hour After Intralipid Infusion)
- Baseline Working Memory(At baseline)
- Post-Intralipid Working Memory(Approximately 1 Hour After Intralipid Infusion)
- Baseline Social Cognition(At baseline)
- Post-Intralipid Social Cognition(Approximately 1 Hour After Intralipid Infusion)
- Baseline Reward Responsiveness(At baseline)
- Post-Intralipid Reward Responsiveness(Approximately 1 Hour After Intralipid Infusion)
研究者
Kelly Cosgrove
Professor of Psychiatry and of Neuroscience and of Radiology and Biomedical Imaging
Yale University