Ignite Creation Date:
2024-05-05 @ 7:27 PM
Last Modification Date:
2024-10-26 @ 9:49 AM
Study NCT ID:
NCT00677911
Status:
COMPLETED
Last Update Posted:
2019-07-26
First Post:
2008-05-13
Brief Title:
Immunologic Response to Negative Cognition in Persons With Chronic Pain
Sponsor:
Oregon Health and Science University
Organization:
Oregon Health and Science University
Study Overview
Official Title:
Immunologic Response to Negative Cognition in Persons With Chronic Pain
Status:
COMPLETED
Status Verified Date:
2019-07
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:
Principal InvestigatorProgram Director Last First Middle Darnall Beth APS Future Leaders in Pain Small Research Grants Application Page 5 Continuation Format Page
Summary Chronic pain is stressful both physically and psychologically Stressful experiences induce autonomic nervous system arousal which reliably leads to inflammation and immune suppression Inflammation then exacerbates existing pain and may be a key factor in both the genesis and maintenance of pain Stress-induced immune effects are detected two hours 2 hrs post-stressor suggesting only a few stressful experiences per day may be sufficient to sustain elevated pain levels1 Cognition has emerged as a potential mediating factor in the relationship between pain and stress Mentally recreating an emotionally stressful event induces de novo physiological stress1 In other words thinking about an emotionally charged event down-regulates autonomic stress responses and subsequent immune effects Therefore exploring cognition as a mediating factor between stress pain and inflammation will inform our understanding of pain pathways as well as improve treatment for pain
Study Rationale The acute stress response induces immunosuppression however this relationship has been studied in arbitrary models only shock avoidance job interview This study employs the novel approach of examining stress and immune responses to a personally relevant stressor pain prior studies used arbitrary models only shock avoidance job interview Pain offers a highly salient and personal context well-suited for investigation of negative cognitive perseveration Pain is acutely sensitive to exacerbation via inflammation and thus the relevance of examining immune effects of rumination on future negative expectations expecting the worst is underscored
Goal To test the biological consequences of negative expectations achieved via an active 10-minute negative cognitive perseveration on a personally relevant stressor future worsening of ones chronic pain condition Biological stress response will be measured via heart rate HR blood pressure BP and serum cortisol Impact of negative cognition on inflammation will be measured using interleukin-1 IL-1 interleukin-6 IL-6 and tumor necrosis factor-alpha TNF-α as biomarkers of immune function controlling for depression and pain catastrophizing This study aims to inform the understanding of pain mechanisms
Aim 1 Determine the magnitude of an autonomic stress response to an induction of negative cognition
Aim 2 Determine immune effects of the experiment-induced stress response
Aim 3 Establish whether a pre-existing tendency to catastrophize mediates the relationship between experiment-induced negative perseveration and immune effects
Aim 4 Establish whether stress-related increases in IL-6 remain elevated post 2 hrs
Summary Chronic pain is stressful both physically and psychologically Stressful experiences induce autonomic nervous system arousal which reliably leads to inflammation and immune suppression Inflammation then exacerbates existing pain and may be a key factor in both the genesis and maintenance of pain Stress-induced immune effects are detected two hours 2 hrs post-stressor suggesting only a few stressful experiences per day may be sufficient to sustain elevated pain levels1 Cognition has emerged as a potential mediating factor in the relationship between pain and stress Mentally recreating an emotionally stressful event induces de novo physiological stress1 In other words thinking about an emotionally charged event down-regulates autonomic stress responses and subsequent immune effects Therefore exploring cognition as a mediating factor between stress pain and inflammation will inform our understanding of pain pathways as well as improve treatment for pain
Study Rationale The acute stress response induces immunosuppression however this relationship has been studied in arbitrary models only shock avoidance job interview This study employs the novel approach of examining stress and immune responses to a personally relevant stressor pain prior studies used arbitrary models only shock avoidance job interview Pain offers a highly salient and personal context well-suited for investigation of negative cognitive perseveration Pain is acutely sensitive to exacerbation via inflammation and thus the relevance of examining immune effects of rumination on future negative expectations expecting the worst is underscored
Goal To test the biological consequences of negative expectations achieved via an active 10-minute negative cognitive perseveration on a personally relevant stressor future worsening of ones chronic pain condition Biological stress response will be measured via heart rate HR blood pressure BP and serum cortisol Impact of negative cognition on inflammation will be measured using interleukin-1 IL-1 interleukin-6 IL-6 and tumor necrosis factor-alpha TNF-α as biomarkers of immune function controlling for depression and pain catastrophizing This study aims to inform the understanding of pain mechanisms
Aim 1 Determine the magnitude of an autonomic stress response to an induction of negative cognition
Aim 2 Determine immune effects of the experiment-induced stress response
Aim 3 Establish whether a pre-existing tendency to catastrophize mediates the relationship between experiment-induced negative perseveration and immune effects
Aim 4 Establish whether stress-related increases in IL-6 remain elevated post 2 hrs
Detailed Description:
Methods This prospective study examines the magnitude of biological stress and subsequent immunologic changes in response to negative cognitive perseveration Five physiological measurement time points occur over the course of the 3 hour experiment
Demographics and health characteristics of interest gender marital status smoking status education level race height weight body mass index medical comorbidity psychological comorbidity medications for inflammation pain or psychiatric conditions
Inclusionary Criteria
18 years of age 65 years of age
Non-inflammatory musculoskeletal patients presenting for evaluation at Oregon Health Science University OHSU Comprehensive Pain Center CPC
Exclusionary Criteria
Active or recent virusinfection
Thought disorder Suicidality
Substance Abuse
Active corticosteroid regimen
Pregnancy
Limited venous access
Former intravenous drug user
Enrollment All persons presenting for evaluation at the CPC who meet study criteria will be offered the option to participate in the study Approximately 60 new pain patients are evaluated by psychology monthly and we expect to obtain our goal of 40 participants within 6 months Informed consent will be obtained in compliance with OHSU Institutional Review Board protocol Subjects will receive 100 gift certificate compensation even if they fail to complete the study We anticipate a low completion failure rate as the study is completed in one 3-hour time block Study times will be standardized to account for circadian effects Participants will be told to arrive having eaten a light breakfast with minimal caffeine consumption eg less than 2 cups of coffee They will be given a subject number and their psychiatric diagnoses will be blinded to prevent bias The study involves gathering 5 serum samples and thus participants will be catheterized by nursing staff to minimize physiological stress
Principal InvestigatorProgram Director Last First Middle Darnall Beth APS Future Leaders in Pain Small Research Grants Application Page 7 Continuation Format Page
Study site The study will be conducted at the NIH-funded General Clinical Research Center GCRC The GCRC provides state of the art resources including research space specialized research nurses to perform blood draws and gather biodata biostatisticians and sophisticated laboratories to perform serum biomarker analysis OHSUs GCRC is Oregons premier multidisciplinary patient-oriented research facility and is housed in the same building as the CPC thus minimizing travel burden on participants
Active Stress Induction Negative Cognitive Perseveration On their experiment day participants will interface with a licensed clinical psychologist who did not perform their clinical interview and who is blinded to their diagnoses The psychologist will instruct the participant talk for 10 minutes about the worst aspects of their pain to discuss their loss of control over their situation the negative impact pain has had on their life and others They will be guided to imagine that their situation will progressively worsen and to focus on how badly they will feel as a result Two measures of induction efficacy will be given subjective verbal rating 0-10 and objective rating by attending psychologist 0-10 The intervention ends at 10 minutes and the remainder of the study involves biodata measurement
Study ends at 25 hrs post induction following the final blood draw The psychologist will debrief subjects and will assess their affective state Their subjective units of distress will be checked Persons who are in a continued negative cognitive state will receive 30 minutes of Cognitive Behavioral Therapy CBT by the on-site psychologist Care will be taken not to allow participants to leave the study site in distress Participants will receive follow up psychology care at the CPC as indicated in their treatment plan
Demographics and health characteristics of interest gender marital status smoking status education level race height weight body mass index medical comorbidity psychological comorbidity medications for inflammation pain or psychiatric conditions
Inclusionary Criteria
18 years of age 65 years of age
Non-inflammatory musculoskeletal patients presenting for evaluation at Oregon Health Science University OHSU Comprehensive Pain Center CPC
Exclusionary Criteria
Active or recent virusinfection
Thought disorder Suicidality
Substance Abuse
Active corticosteroid regimen
Pregnancy
Limited venous access
Former intravenous drug user
Enrollment All persons presenting for evaluation at the CPC who meet study criteria will be offered the option to participate in the study Approximately 60 new pain patients are evaluated by psychology monthly and we expect to obtain our goal of 40 participants within 6 months Informed consent will be obtained in compliance with OHSU Institutional Review Board protocol Subjects will receive 100 gift certificate compensation even if they fail to complete the study We anticipate a low completion failure rate as the study is completed in one 3-hour time block Study times will be standardized to account for circadian effects Participants will be told to arrive having eaten a light breakfast with minimal caffeine consumption eg less than 2 cups of coffee They will be given a subject number and their psychiatric diagnoses will be blinded to prevent bias The study involves gathering 5 serum samples and thus participants will be catheterized by nursing staff to minimize physiological stress
Principal InvestigatorProgram Director Last First Middle Darnall Beth APS Future Leaders in Pain Small Research Grants Application Page 7 Continuation Format Page
Study site The study will be conducted at the NIH-funded General Clinical Research Center GCRC The GCRC provides state of the art resources including research space specialized research nurses to perform blood draws and gather biodata biostatisticians and sophisticated laboratories to perform serum biomarker analysis OHSUs GCRC is Oregons premier multidisciplinary patient-oriented research facility and is housed in the same building as the CPC thus minimizing travel burden on participants
Active Stress Induction Negative Cognitive Perseveration On their experiment day participants will interface with a licensed clinical psychologist who did not perform their clinical interview and who is blinded to their diagnoses The psychologist will instruct the participant talk for 10 minutes about the worst aspects of their pain to discuss their loss of control over their situation the negative impact pain has had on their life and others They will be guided to imagine that their situation will progressively worsen and to focus on how badly they will feel as a result Two measures of induction efficacy will be given subjective verbal rating 0-10 and objective rating by attending psychologist 0-10 The intervention ends at 10 minutes and the remainder of the study involves biodata measurement
Study ends at 25 hrs post induction following the final blood draw The psychologist will debrief subjects and will assess their affective state Their subjective units of distress will be checked Persons who are in a continued negative cognitive state will receive 30 minutes of Cognitive Behavioral Therapy CBT by the on-site psychologist Care will be taken not to allow participants to leave the study site in distress Participants will receive follow up psychology care at the CPC as indicated in their treatment plan
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