Back to resultsNeuroimmune Mechanisms in Obesity
Primary Purpose
Obesity
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intralipid Infusion
Sponsored by
About this trial
This is an interventional basic science trial for Obesity
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Sites / Locations
- Yale University
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Baseline [11C]PBR28 PET Scan
Post-Intralipid Infusion [11C]PBR28 PET Scan
Arm Description
Subjects will complete a 120-minute baseline [11C]PBR28 PET scan.
Subjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion
Outcomes
Primary Outcome Measures
Baseline [11C]PBR28 VT values
[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
[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
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
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
Regional [11C]PBR28 VT values from pre-lipid infusion PET Scan
Post-Intralipid Microglial Activation
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
Secondary Outcome Measures
Baseline Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Post-Intralipid Infusion Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Baseline Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Post-Intralipid Infusion Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Baseline Verbal Memory
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Post-Intralipid Verbal Memory
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Baseline Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Post-Intralipid Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Baseline Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Post-Intralipid Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Baseline Working Memory
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Post-Intralipid Working Memory
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Baseline Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Post-Intralipid Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Baseline Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Post-Intralipid Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05553405
Brief Title
Neuroimmune Mechanisms in Obesity
Official Title
Neuroimmune Mechanisms in Obesity
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Withdrawn
Why Stopped
No longer able to run study
Study Start Date
January 1, 2024 (Anticipated)
Primary Completion Date
January 1, 2033 (Anticipated)
Study Completion Date
January 1, 2033 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yale University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Baseline [11C]PBR28 PET Scan
Arm Type
No Intervention
Arm Description
Subjects will complete a 120-minute baseline [11C]PBR28 PET scan.
Arm Title
Post-Intralipid Infusion [11C]PBR28 PET Scan
Arm Type
Experimental
Arm Description
Subjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion
Intervention Type
Drug
Intervention Name(s)
Intralipid Infusion
Intervention Description
Intralipid 20% (a 20% IV fat emulsion) is a sterile, non-pyrogenic fat emulsion prepared for IV administration as a source of calories and essential fatty acids. It is made up of 20% soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin and water for injection. In addition, sodium hydroxide has been added to adjust the pH so that the final product pH is 8.
Primary Outcome Measure Information:
Title
Baseline [11C]PBR28 VT values
Description
[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.
Time Frame
At baseline
Title
Post-Intralipid [11C]PBR28 VT values
Description
[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.
Time Frame
Approximately 3 Hours After Intralipid Infusion
Title
Baseline Functional Connectivity
Description
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.
Time Frame
At baseline
Title
Post-Intralipid Functional Connectivity
Description
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.
Time Frame
Approximately 3 Hours After Intralipid Infusion
Title
Baseline Microglial Activation
Description
Regional [11C]PBR28 VT values from pre-lipid infusion PET Scan
Time Frame
At baseline
Title
Post-Intralipid Microglial Activation
Description
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
Time Frame
Approximately 3 Hours After Intralipid Infusion
Secondary Outcome Measure Information:
Title
Baseline Visual Attention
Description
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Time Frame
At baseline
Title
Post-Intralipid Infusion Visual Attention
Description
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Visual Learning
Description
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Time Frame
At baseline
Title
Post-Intralipid Infusion Visual Learning
Description
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Verbal Memory
Description
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Time Frame
At baseline
Title
Post-Intralipid Verbal Memory
Description
Verbal memory: # of correctly recalled items from a grocery list (3 trials). Verbal recall: # of correctly recalled items from a grocery list after a delay (1 trial; higher ~ better memory/recall).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Executive Function
Description
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Time Frame
At baseline
Title
Post-Intralipid Executive Function
Description
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Visual-Motor Processing Speed
Description
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Time Frame
At baseline
Title
Post-Intralipid Visual-Motor Processing Speed
Description
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Working Memory
Description
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Time Frame
At baseline
Title
Post-Intralipid Working Memory
Description
Working memory: % of correctly identified cards that matched the card presented either one- or two-cards previously (arcsine(% correct); higher ~ better working memory).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Social Cognition
Description
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Time Frame
At baseline
Title
Post-Intralipid Social Cognition
Description
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Time Frame
Approximately 1 Hour After Intralipid Infusion
Title
Baseline Reward Responsiveness
Description
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Time Frame
At baseline
Title
Post-Intralipid Reward Responsiveness
Description
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Time Frame
Approximately 1 Hour After Intralipid Infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kelly Cosgrove, PhD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Neuroimmune Mechanisms in Obesity
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