Ignite Creation Date:
2024-05-06 @ 2:26 PM
Last Modification Date:
2024-10-26 @ 1:30 PM
Study NCT ID:
NCT04310423
Status:
COMPLETED
Last Update Posted:
2024-03-15
First Post:
2020-03-11
Brief Title:
An Inflammatory Challenge Using Endotoxin
Sponsor:
University of California Los Angeles
Organization:
University of California Los Angeles
Study Overview
Official Title:
An Inflammatory Challenge Using Endotoxin
Status:
COMPLETED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study design consists of a randomized double-blind placebo-controlled trial of low dose endotoxin The low dose endotoxin challenge induces a transient systemic inflammatory response with normalization of cytokine levels within hours This phasic inflammation is distinct from chronic tonic levels of inflammation that may be present with AUD A total of 38 non-treatment seeking heavy drinking men and women and 38 light drinking healthy controls will participate in the study Recruitment will be monitored to ensure the two groups are matched by gender Eligible participants will be randomly assigned stratified by gender and BDI-II severity to receive a single IV infusion of either low dose endotoxin 08 ngkg of body weight or placebo same volume of 09 saline solution at the UCLA Outpatient Clinical and Translational Research Center CTRC All participants will complete an alcohol cue-exposure paradigm and reward responsiveness assessment 2 hours post infusion which is the time of expected peak cytokine response All participants will also complete an fMRI alcohol cue-reactivity paradigm at 3 hours post infusion Plasma levels of proinflammatory cytokines ie Interleukin-6 IL-6 and tumor necrosis factor-α TNF- α mood and alcohol craving will be assessed at baseline and then hourly for four hours post infusion
Detailed Description:
RECRUITMENT Participants will be recruited from the community through online and newspaper advertisements Campaigns in local buses and print publications eg LA Weekly will also be implemented Targeted recruitment will also take place through a lab database of previous study participants who agreed to be contacted for future studies
TELEPHONE SCREEN Individuals who call the lab in response to flyers and advertisements expressing interest in the study will receive detailed information about the study procedures and if they remain interested they will complete a telephone screen performed by a trained research assistant for self-reported inclusion and exclusion criteria Those who appear eligible will be invited to the laboratory for an initial in-person screening session
INITIAL SCREENING Prior to conducting any research related procedures research staff will conduct the informed consent process which details the procedures to take place during the screening visit Informed consent will be a three part process First participants will be asked to read and provide verbal consent for breathalyzer If the breathalyzer is above 0000 the visit will be stopped and the participant will not be compensated The participant will be given an opportunity to reschedule the visit for another day If the breathalyzer test is negative the written informed consent form will be reviewed and signed by the participant and study staff outlining procedures for the initial screening visit A second written consent form will be reviewed and signed in the presence of the study physician at the medical screening visit if the participant is found eligible to continue to that visit At the initial screening visit subjects will be asked to provide a urine sample to test for drugs of abuse and pregnancy if female and will complete a series of individual differences measures described in detail below This visit should take approximately 2 hours Following the initial in-person screening the study coordinator will meet with the PI to determine if the participant is eligible to continue to the medical screening based on study inclusionexclusion criteria
MEDICAL SCREENING Those participants who appear to be eligible after the initial screening visit will then be scheduled for a second screening visit This visit will be conducted by the study physician and will start with a breathalyzer test If the breathalyzer is above 0000 the visit will be stopped and the participant will not be compensated The participant will be given an opportunity to reschedule the visit for another day If the breathalyzer test is negative the physician will conduct the second written experimental consent medical history interview and physical exam In addition a urine drug screen test will be repeated The participant will then be accompanied by research personnel to the CTRC for blood specimen collection including Comprehensive Metabolic Panel and Complete Blood Count to evaluate overall health and EKG to screen for medical conditions that could make study participation medically unsafe The study physician will review each participants medical history vital signs weight review of systems and laboratory tests including liver function tests LFTs drug screen chemistry screen and urine pregnancy screen to determine if it is medically safe for the participant to take the study medication Any subject who is excluded from the study will be compensated for their time in the screening session and will be offered referrals for alcohol treatment in the community
RANDOMIZATIONINFLAMMATORY CHALLENGE Upon arrival to the CTRC eligibility for the inflammatory challenge will be reviewed to ensure that none of the exclusion criteria have been met as described above A nurse who will be blind to the condition will insert a catheter with a heparin lock into the non-dominant forearm for drug administration and hourly blood draws Each participant will be randomly assigned to receive either low-dose endotoxin 08 ngkg of body weight administered or placebo same volume of 09 saline which will be administered by the nurse as an intravenous bolus The endotoxin will be derived from Escherichia coli E Coli group O113 BB-IND 12948 to MRI and will be provided by the National Institutes of Health Clinical Center as a reference endotoxin for studies of experimental inflammation in humans Participants will complete assessments as outlined below at baseline and every hour for 4 hours post-infusion One standard meal and one snack will be provided by the CTRC to each participant during the experimental visit At the end of the experimental period participants will have the catheter removed and will be discharged with instructions to abstain from consuming alcohol for 24 hours after discharge A follow-up phone call by the study physician will be conducted the day after the inflammatory challenge and again 1-2 weeks later to assess for any adverse events
The study physician Dr Miotto will be on-call and will manage any adverse events during the inflammatory challenge She will consult with Dr Irwin Co-I as needed to manage adverse events In the event that significant medical problems are encountered the blind will be broken and appropriate medical treatment will be provided Individuals who meet the following stopping criteria will discontinue study-related data collection procedures cytokine assays and cue exposure paradigm
1 1 SAE at least possibly related to endotoxin administration
2 2 Grade 3 severe adverse events at least possibly related to endotoxin administration based on the FDA Guidance Document Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials ALCOHOL CUE REACTIVITY SESSION CR Approximately 2 hours after receiving intravenous endotoxin or matched placebo participants will complete the cue-exposure paradigm Alcohol cue exposure will follow well-established experimental procedures Sessions will begin with a 3-minute relaxation period Participants will then hold and smell a glass of water for 3 minutes to control for the effects of simple exposure to any potable liquid Next participants will hold and smell a glass of their preferred alcoholic beverage for 3 minutes Order is not counterbalanced because of carryover effects that are known to occur Participants who are smokers will be allowed a smoke break immediately prior to and immediately after the CR assessment After every 3 minute period participants will rate their urge to drink on the Alcohol Urge Questionnaire
REWARD RESPONSIVENESS Approximately 2 hours after receiving intravenous endotoxin or matched placebo participants will complete the reward responsiveness paradigm including the Probabilistic Reward Task PRT and Reward Responsiveness Scale RRS The PRT is a 25-minute task that will be administered at baseline and hour 2 The task assesses behavioral modulation as a function of reward-based reinforcement ie reward seeking by asking participants to respond to stimuli eliciting a response bias by introducing an asymmetric reinforcer ratio The RRS is a self-report questionnaire that measures reward responsiveness by asking subjects to rate their agreement with various statements on a 4-point Likert scale
NEUROIMAGING CUE-REACTIVITY fMRI Approximately 3 hours after receiving intravenous endotoxin or matched placebo participants will complete a functional magnetic resonance imaging fMRI scan This scan will include an fMRI visual alcohol cue-reactivity paradigm which will follow well-established procedures The alcohol cues task consists of viewing visual alcohol negative and neutral cues presented in six 120-s epochs total scan duration 12 minutes with each epoch consisting of four 24-s blocks one block of alcohol cues one block of neutral cues one block of negative images and one block of fixation Alcohol blocks will be specific to beverage type beer wine or liquor with two blocks of each beverage type Prior to scanning participants will rate their craving on a four-point scale and will also provide ratings of their craving immediately following each cue block
TELEPHONE SCREEN Individuals who call the lab in response to flyers and advertisements expressing interest in the study will receive detailed information about the study procedures and if they remain interested they will complete a telephone screen performed by a trained research assistant for self-reported inclusion and exclusion criteria Those who appear eligible will be invited to the laboratory for an initial in-person screening session
INITIAL SCREENING Prior to conducting any research related procedures research staff will conduct the informed consent process which details the procedures to take place during the screening visit Informed consent will be a three part process First participants will be asked to read and provide verbal consent for breathalyzer If the breathalyzer is above 0000 the visit will be stopped and the participant will not be compensated The participant will be given an opportunity to reschedule the visit for another day If the breathalyzer test is negative the written informed consent form will be reviewed and signed by the participant and study staff outlining procedures for the initial screening visit A second written consent form will be reviewed and signed in the presence of the study physician at the medical screening visit if the participant is found eligible to continue to that visit At the initial screening visit subjects will be asked to provide a urine sample to test for drugs of abuse and pregnancy if female and will complete a series of individual differences measures described in detail below This visit should take approximately 2 hours Following the initial in-person screening the study coordinator will meet with the PI to determine if the participant is eligible to continue to the medical screening based on study inclusionexclusion criteria
MEDICAL SCREENING Those participants who appear to be eligible after the initial screening visit will then be scheduled for a second screening visit This visit will be conducted by the study physician and will start with a breathalyzer test If the breathalyzer is above 0000 the visit will be stopped and the participant will not be compensated The participant will be given an opportunity to reschedule the visit for another day If the breathalyzer test is negative the physician will conduct the second written experimental consent medical history interview and physical exam In addition a urine drug screen test will be repeated The participant will then be accompanied by research personnel to the CTRC for blood specimen collection including Comprehensive Metabolic Panel and Complete Blood Count to evaluate overall health and EKG to screen for medical conditions that could make study participation medically unsafe The study physician will review each participants medical history vital signs weight review of systems and laboratory tests including liver function tests LFTs drug screen chemistry screen and urine pregnancy screen to determine if it is medically safe for the participant to take the study medication Any subject who is excluded from the study will be compensated for their time in the screening session and will be offered referrals for alcohol treatment in the community
RANDOMIZATIONINFLAMMATORY CHALLENGE Upon arrival to the CTRC eligibility for the inflammatory challenge will be reviewed to ensure that none of the exclusion criteria have been met as described above A nurse who will be blind to the condition will insert a catheter with a heparin lock into the non-dominant forearm for drug administration and hourly blood draws Each participant will be randomly assigned to receive either low-dose endotoxin 08 ngkg of body weight administered or placebo same volume of 09 saline which will be administered by the nurse as an intravenous bolus The endotoxin will be derived from Escherichia coli E Coli group O113 BB-IND 12948 to MRI and will be provided by the National Institutes of Health Clinical Center as a reference endotoxin for studies of experimental inflammation in humans Participants will complete assessments as outlined below at baseline and every hour for 4 hours post-infusion One standard meal and one snack will be provided by the CTRC to each participant during the experimental visit At the end of the experimental period participants will have the catheter removed and will be discharged with instructions to abstain from consuming alcohol for 24 hours after discharge A follow-up phone call by the study physician will be conducted the day after the inflammatory challenge and again 1-2 weeks later to assess for any adverse events
The study physician Dr Miotto will be on-call and will manage any adverse events during the inflammatory challenge She will consult with Dr Irwin Co-I as needed to manage adverse events In the event that significant medical problems are encountered the blind will be broken and appropriate medical treatment will be provided Individuals who meet the following stopping criteria will discontinue study-related data collection procedures cytokine assays and cue exposure paradigm
1 1 SAE at least possibly related to endotoxin administration
2 2 Grade 3 severe adverse events at least possibly related to endotoxin administration based on the FDA Guidance Document Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials ALCOHOL CUE REACTIVITY SESSION CR Approximately 2 hours after receiving intravenous endotoxin or matched placebo participants will complete the cue-exposure paradigm Alcohol cue exposure will follow well-established experimental procedures Sessions will begin with a 3-minute relaxation period Participants will then hold and smell a glass of water for 3 minutes to control for the effects of simple exposure to any potable liquid Next participants will hold and smell a glass of their preferred alcoholic beverage for 3 minutes Order is not counterbalanced because of carryover effects that are known to occur Participants who are smokers will be allowed a smoke break immediately prior to and immediately after the CR assessment After every 3 minute period participants will rate their urge to drink on the Alcohol Urge Questionnaire
REWARD RESPONSIVENESS Approximately 2 hours after receiving intravenous endotoxin or matched placebo participants will complete the reward responsiveness paradigm including the Probabilistic Reward Task PRT and Reward Responsiveness Scale RRS The PRT is a 25-minute task that will be administered at baseline and hour 2 The task assesses behavioral modulation as a function of reward-based reinforcement ie reward seeking by asking participants to respond to stimuli eliciting a response bias by introducing an asymmetric reinforcer ratio The RRS is a self-report questionnaire that measures reward responsiveness by asking subjects to rate their agreement with various statements on a 4-point Likert scale
NEUROIMAGING CUE-REACTIVITY fMRI Approximately 3 hours after receiving intravenous endotoxin or matched placebo participants will complete a functional magnetic resonance imaging fMRI scan This scan will include an fMRI visual alcohol cue-reactivity paradigm which will follow well-established procedures The alcohol cues task consists of viewing visual alcohol negative and neutral cues presented in six 120-s epochs total scan duration 12 minutes with each epoch consisting of four 24-s blocks one block of alcohol cues one block of neutral cues one block of negative images and one block of fixation Alcohol blocks will be specific to beverage type beer wine or liquor with two blocks of each beverage type Prior to scanning participants will rate their craving on a four-point scale and will also provide ratings of their craving immediately following each cue block
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None