Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06618716
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
None
First Post:
2024-09-12
Brief Title:
Individual Differences in Acute Response to Experimental Inflammation Microcirculatory Changes and Psychological Predictors
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Individual Differences in the Acute Response to Experimentally Induced Inflammation Microcirculatory Changes and Psychological Predictors
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The physiological and behavioral responses to inflammatory vary greatly between individuals The knowlegde about what causes these differences is sparse but plausible explanations are variations in sensitivity to peripheral inflammation The goal of the study is to understand microcirculatory changes in skin and their possible correlation with conventional measurements of sickness and disease in humans A better understanding of possible psychological predictors of sickness behaviour is also warranted as it may affect the results
The general aim of the study is to assess microcirculatory changes in skin of the face chest hands and feet using different optical imaging techniques and to identify psychological predictors in the acute behavioral response to experimentally induced inflammation The participants are healthy volunteers in the age of 18-40 years of both sexgenders The main questions to answer are
1 How do acute inflammation change microcirculation in the skin as measured by temperature red blood cell concentration blood flow and spectral changes correlated with fluids and other proteins
2 Can a stronger behavioral response to experimental endotoxemia be predicted by psychological factors of the individuals
It is a blinded with-in subject crossover design where the participants will receive placebo-injection with saline on one study day and LPS-injection the other study day in a randomized order
Participants will on the study days
Fill in psychometric questionnaires
Be measured with bio-optical imaging methods at regular intervalls
Be monitored with regular medical parameters such as blood pressure oxygen saturation puls etc When the volunteers feel recovered and the medical staff are confident of the recovery the volunteers will be discharged
The general aim of the study is to assess microcirculatory changes in skin of the face chest hands and feet using different optical imaging techniques and to identify psychological predictors in the acute behavioral response to experimentally induced inflammation The participants are healthy volunteers in the age of 18-40 years of both sexgenders The main questions to answer are
1 How do acute inflammation change microcirculation in the skin as measured by temperature red blood cell concentration blood flow and spectral changes correlated with fluids and other proteins
2 Can a stronger behavioral response to experimental endotoxemia be predicted by psychological factors of the individuals
It is a blinded with-in subject crossover design where the participants will receive placebo-injection with saline on one study day and LPS-injection the other study day in a randomized order
Participants will on the study days
Fill in psychometric questionnaires
Be measured with bio-optical imaging methods at regular intervalls
Be monitored with regular medical parameters such as blood pressure oxygen saturation puls etc When the volunteers feel recovered and the medical staff are confident of the recovery the volunteers will be discharged
Detailed Description:
Background Acute illness manifest itself not only by physiological responses such as eg fever pain and nausea but is often accompanied by psychological and behavioral changes such as sleepwake disturbances fatigue loss of appetite and depression The physiological and behavioral responses to inflammatory activation vary greatly between individuals The knowledge about what causes these differences is sparse but plausible explanations are variations in sensitivity to peripheral inflammation and inflammation-induced brain changes As the skin is readily accessible it provides an appropriate site to assess microvascular reactivity during inflammation Moreover recent technological advances have provided simple and non-invasive methods to assess skin microvascular function Therefore human cutaneous circulation could be used as a surrogate marker of systemic microvascular function in inflammation In the present study we use experimentally induced immunological activation in healthy humans to study microcirculatory skin changes as well as behavioral predictors of individual sensitivity to an acute inflammatory stimulus
The model of experimental endotoxemia to induce acute inflammation The model of experimental endotoxemia is a well-accepted and frequently used model to study the neuropsychiatric effects of pro-inflammatory cytokines both in animals and in humans The model is based on the sterile activation of the immune system obtained by intravenous injection of an endotoxin lipopolysaccharide LPS a wall component of gram-negative bacteria such as E coli Injection of LPS will affect the functionality of the vascular endothelium Positioned at the interface between circulating blood and surrounding tissue endothelial cells which line the inner walls of blood vessels play a crucial role in the response to pathogens The endothelium serves various functions essential for maintaining organ homeostasis including vasoregulation selective vascular permeability and providing an anticoagulant surface However during infection the normal physiological functions of the endothelium are disrupted contributing to the organ failure characteristic of sepsis Importantly the response to inflammation during experimental endotoxemia differs substantially across individuals This holds for the degree of increase in inflammatory cytokines the neural response as well as the behavioral changes that entail inflammation It should be noted that the neuropsychiatric response to inflammation is not explained fully by the magnitude of the inflammatory response indicating that other factors are involved Recent research points toward the importance of top-down mechanisms in modifying the effect of inflammation on behavior Such mechanisms might include pre-existent emotional status and beliefs about the intensity of which one will become sick after an infection Identifying the predictors of a heightened behavioral response to inflammation would help identifying markers of inflammation-associated neuropsychiatric vulnerability but this has rarely been investigated
General aim The general aim of the study is to assess microcirculatory changes in skin of the face chest hands and feet using different optical imaging techniques and to identify psychological predictors in the acute behavioral response to experimentally induced inflammation
Primary research questions
The main research questions are
1 to assess how acute inflammation affects
the microcirculation in skin such as face chest arms hands and feet as investigated with different non-invasive optical imaging techniques
Core temperature changes
Facial temperature changes
Changes in equivalents to red blood cell concentration and blood flow
Spectral changes in skin possibly correlated with fluids and other proteins affected by microcirculatory changes
2 to assess whether a stronger behavioral response ie sickness behavior negative mood fatigue anxiety pain to experimental endotoxemia is predicted by
higher interoceptive sensitivity as measured by self-report and an objective task heartrate discrimination task
less cognitive resilience ie self-efficacy optimism perseverance coping strategies ability to update beliefs in the fact of contradictory evidence
worse baseline emotional status ie trait anxiety fatigue perceived stress
stronger health anxiety and disgust tendencies
Sociocultural factors that have been found to relate to sickness behavior such as stoic endurance of pain and discomfort familism individualism and collectivism
baseline biological motion pattern walking speed rigidity of gait and slumped posture
Methods Research principals The research principals are Region Östergötland Karolinska Institutet and Stockholm University Sweden Data collection will be conducted at the Emergency Medicine Research Center EMRC Processing of data will be conducted at EMRC Region Östergötland Karolinska Institutet and Stockholm University
Study design The study will be conducted at the Emergency Medicine Research Center at the University Hospital of Linköping The study will follow a double-blind within-subject crossover placebo-controlled design All subjects will receive an intravenous administration of LPS at a dose of up to 08 ngkg body weight once and an intravenous administration of placebo once in a randomized order and with at least 4 weeks of wash-out period Upon arrival volunteers will be placed on a hospital bed in a single room and a catheter will be placed in the forearm or hand to avoid multiple needle insertion A urine sample for pregnancy testing and drug screening will be obtained for safety reasons The participants will then complete the baseline questionnaires and the baseline blood sample will be drawn After the baseline assessments volunteers will receive the LPS or placebo injection Vital signs pulse blood pressure blood-oxygen saturation respiratory frequency will be continuously monitored and recorded at 30-minute intervals Body temperature will be monitored and recorded every 30 minutes with regular tympanic thermometer as well as continuously using bio-optical imaging techniques Blood samples will be taken approximately every hour to measure the inflammatory response see assessments - inflammatory markers from blood samples below Bio-optical imaging will be performed once before injection and at several occasions after the injection Web-based questionnaires will be completed regularly to measure the sickness and emotional response will be completed by the participants just after acquisition of blood samples Several behavioral tasks will be conducted during the study day Volunteers will be discharged 6-10 hrs or when considered recovered by medical staff after the injection following a medical examination
The model of experimental endotoxemia to induce acute inflammation The model of experimental endotoxemia is a well-accepted and frequently used model to study the neuropsychiatric effects of pro-inflammatory cytokines both in animals and in humans The model is based on the sterile activation of the immune system obtained by intravenous injection of an endotoxin lipopolysaccharide LPS a wall component of gram-negative bacteria such as E coli Injection of LPS will affect the functionality of the vascular endothelium Positioned at the interface between circulating blood and surrounding tissue endothelial cells which line the inner walls of blood vessels play a crucial role in the response to pathogens The endothelium serves various functions essential for maintaining organ homeostasis including vasoregulation selective vascular permeability and providing an anticoagulant surface However during infection the normal physiological functions of the endothelium are disrupted contributing to the organ failure characteristic of sepsis Importantly the response to inflammation during experimental endotoxemia differs substantially across individuals This holds for the degree of increase in inflammatory cytokines the neural response as well as the behavioral changes that entail inflammation It should be noted that the neuropsychiatric response to inflammation is not explained fully by the magnitude of the inflammatory response indicating that other factors are involved Recent research points toward the importance of top-down mechanisms in modifying the effect of inflammation on behavior Such mechanisms might include pre-existent emotional status and beliefs about the intensity of which one will become sick after an infection Identifying the predictors of a heightened behavioral response to inflammation would help identifying markers of inflammation-associated neuropsychiatric vulnerability but this has rarely been investigated
General aim The general aim of the study is to assess microcirculatory changes in skin of the face chest hands and feet using different optical imaging techniques and to identify psychological predictors in the acute behavioral response to experimentally induced inflammation
Primary research questions
The main research questions are
1 to assess how acute inflammation affects
the microcirculation in skin such as face chest arms hands and feet as investigated with different non-invasive optical imaging techniques
Core temperature changes
Facial temperature changes
Changes in equivalents to red blood cell concentration and blood flow
Spectral changes in skin possibly correlated with fluids and other proteins affected by microcirculatory changes
2 to assess whether a stronger behavioral response ie sickness behavior negative mood fatigue anxiety pain to experimental endotoxemia is predicted by
higher interoceptive sensitivity as measured by self-report and an objective task heartrate discrimination task
less cognitive resilience ie self-efficacy optimism perseverance coping strategies ability to update beliefs in the fact of contradictory evidence
worse baseline emotional status ie trait anxiety fatigue perceived stress
stronger health anxiety and disgust tendencies
Sociocultural factors that have been found to relate to sickness behavior such as stoic endurance of pain and discomfort familism individualism and collectivism
baseline biological motion pattern walking speed rigidity of gait and slumped posture
Methods Research principals The research principals are Region Östergötland Karolinska Institutet and Stockholm University Sweden Data collection will be conducted at the Emergency Medicine Research Center EMRC Processing of data will be conducted at EMRC Region Östergötland Karolinska Institutet and Stockholm University
Study design The study will be conducted at the Emergency Medicine Research Center at the University Hospital of Linköping The study will follow a double-blind within-subject crossover placebo-controlled design All subjects will receive an intravenous administration of LPS at a dose of up to 08 ngkg body weight once and an intravenous administration of placebo once in a randomized order and with at least 4 weeks of wash-out period Upon arrival volunteers will be placed on a hospital bed in a single room and a catheter will be placed in the forearm or hand to avoid multiple needle insertion A urine sample for pregnancy testing and drug screening will be obtained for safety reasons The participants will then complete the baseline questionnaires and the baseline blood sample will be drawn After the baseline assessments volunteers will receive the LPS or placebo injection Vital signs pulse blood pressure blood-oxygen saturation respiratory frequency will be continuously monitored and recorded at 30-minute intervals Body temperature will be monitored and recorded every 30 minutes with regular tympanic thermometer as well as continuously using bio-optical imaging techniques Blood samples will be taken approximately every hour to measure the inflammatory response see assessments - inflammatory markers from blood samples below Bio-optical imaging will be performed once before injection and at several occasions after the injection Web-based questionnaires will be completed regularly to measure the sickness and emotional response will be completed by the participants just after acquisition of blood samples Several behavioral tasks will be conducted during the study day Volunteers will be discharged 6-10 hrs or when considered recovered by medical staff after the injection following a medical examination
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None