ObesityPhase 1NCT05553405
Neuroimmune Mechanisms in Obesity
A Phase 1 study testing Intralipid Infusion in people with Obesity, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Intralipid Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2024to 1 Jan 2033
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Conditions
- Obesity
- Being tested
- Intralipid Infusion
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid InfusionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Baseline [11C]PBR28 PET Scan | No intervention | Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. |
| Post-Intralipid Infusion [11C]PBR28 PET Scan | Experimental | Subjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion Receives: Drug: Intralipid Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline
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.
Measured: Approximately 3 Hours After Intralipid Infusion
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.
Measured: At baseline
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.
Measured: Approximately 3 Hours After Intralipid Infusion
Baseline Microglial Activation
Regional [11C]PBR28 VT values from pre-lipid infusion PET Scan
Measured: At baseline
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
Measured: Approximately 3 Hours After Intralipid Infusion
Secondary outcomes (16)
Baseline Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Measured: At baseline
Post-Intralipid Infusion Visual Attention
Visual attention: response latency to identify card color (log10(ms); higher ~ worse attention).
Measured: Approximately 1 Hour After Intralipid Infusion
Baseline Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Measured: At baseline
Post-Intralipid Infusion Visual Learning
Visual learning: % of correctly identified repeat cards (arcsine(% correct); higher values ~ better learning).
Measured: Approximately 1 Hour After Intralipid Infusion
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).
Measured: At baseline
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).
Measured: Approximately 1 Hour After Intralipid Infusion
Baseline Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Measured: At baseline
Post-Intralipid Executive Function
Executive function: number of errors navigating a 'hidden' maze (5 trials; higher ~ worse executive function).
Measured: Approximately 1 Hour After Intralipid Infusion
Baseline Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Measured: At baseline
Post-Intralipid Visual-Motor Processing Speed
Visual-motor processing speed: response latency to detect a card flipped over (log10(ms); higher ~ worse processing speed).
Measured: Approximately 1 Hour After Intralipid Infusion
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).
Measured: At baseline
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).
Measured: Approximately 1 Hour After Intralipid Infusion
Baseline Social Cognition
Social cognition: response latency to identify the mismatched facial expression based on its emotional content (ms; log10; higher ~ worse social cognition).
Measured: At baseline
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).
Measured: Approximately 1 Hour After Intralipid Infusion
Baseline Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Measured: At baseline
Post-Intralipid Reward Responsiveness
Reward responsiveness will be quantified via computerized Probabilistic Reward Task
Measured: Approximately 1 Hour After Intralipid Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2022
- Study start1 Jan 2024 (estimated)
- Primary completion1 Jan 2033 (estimated)
- Study completion1 Jan 2033 (estimated)
Why it stopped: No longer able to run study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kelly Cosgrove, Yale University
- Investigators
- Kelly Cosgrove, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05553405
- Sponsor's protocol ID
- 2000031993
- Status last verified
- Jun 2023
- First submitted
- 20 Sep 2022
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroimmune Mechanisms in Obesity
- ClinicalTrials.gov ID
- NCT05553405
- Acronym / sponsor ID
- 2000031993
- Conditions
- Obesity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No longer able to run study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 1 Jan 2033 (estimated)
- Study completion
- 1 Jan 2033 (estimated)
- First posted
- 23 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baseline [11C]PBR28 PET Scan | No intervention | –Subjects will complete a 120-minute baseline [11C]PBR28 PET scan. |
| Post-Intralipid Infusion [11C]PBR28 PET Scan | Experimental | Drug: Intralipid InfusionSubjects will complete a second 120-minute [11C]PBR28 PET scan 4 hours after Intralipid Infusion |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intralipid InfusionIntralipid 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. | Drug | Post-Intralipid Infusion [11C]PBR28 PET Scan |
Primary outcome
Baseline [11C]PBR28 VT values
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: At baseline
Regional [11C]PBR28 VT values from pre-lipid infusion PET Scan
Post-Intralipid Microglial Activation
Time frame: 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
16 secondary outcomes
Baseline Visual Attention
Time frame: At baseline
Post-Intralipid Infusion Visual Attention
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Visual Learning
Time frame: At baseline
Post-Intralipid Infusion Visual Learning
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Verbal Memory
Time frame: At baseline
Post-Intralipid Verbal Memory
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Executive Function
Time frame: At baseline
Post-Intralipid Executive Function
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Visual-Motor Processing Speed
Time frame: At baseline
Post-Intralipid Visual-Motor Processing Speed
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Working Memory
Time frame: At baseline
Post-Intralipid Working Memory
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Social Cognition
Time frame: At baseline
Post-Intralipid Social Cognition
Time frame: Approximately 1 Hour After Intralipid Infusion
Baseline Reward Responsiveness
Time frame: At baseline
Post-Intralipid Reward Responsiveness
Time frame: Approximately 1 Hour After Intralipid Infusion
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kelly Cosgrove, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Intralipid Infusion in people with Obesity, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline [11C]PBR28 VT values (time frame: At baseline). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.