Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06418295
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-17
First Post:
2024-05-13
Brief Title:
Cytokine Alterations and Chronic Post-Surgical Pain
Sponsor:
Lawson Health Research Institute
Organization:
Lawson Health Research Institute
Study Overview
Official Title:
Cytokine Alterations Associated With Persistent Post-surgical Pain and Their Regulation Through Epigenetic Changes - A Pilot Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
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:
Chronic Post-Surgical Pain CPSP is a condition that involves experiencing pain andor discomfort that lasts for more than 3 months following surgery without any explainable cause of this pain such chronic infection or pain caused from a condition preceding surgery This condition negatively impacts health related quality of life and is associated with significant financial burden both for the patient and health care system Patients undergoing common surgeries such as amputation breast surgery hernia repair coronary artery bypass and caesarean section can be prone to developing CPSP CPSP may be caused by the release and expression of different cellular molecules called cytokines and chemokines that can cause a pain response when they are present in the body at certain levels After surgical incision tissue cells have been shown to release cytokines and chemokines thus increasing the concentration of these molecules in the patients blood It is not entirely known what mechanisms cause the increased expression of chemokines and cytokines One method that may play a role in in this expression is epigenetics which is the alteration of gene expression without permanently altering the structure of DNA Unlike mutations epigenetic changes are dynamic possibly reversible and are influenced by environmental and behavioral changes such as diet exercise disease stress toxin exposure etc Epigenetic changes occur all throughout our life and have been associated with several disease processes such as cancer diabetic complications and chronic pain At the molecular level certain events take place that can regulate increase or decrease the expression of cytokines and chemokines most notably DNA methylation of their promotor which involves adding molecules to DNA that does not change its structure but changes its activity The investigators are conducting this study to determine if the alteration of specific cytokines are associated with the occurrence of CPSP and whether these cytokines are regulated by DNA methylation at their promoter This study will take place at London Health Sciences Centre and will recruit up to 60 patients who will be undergoing a thoracotomy procedure surgery of the chest area
Detailed Description:
Chronic Post-Surgical Pain CPSP defined by the International Association for the Study of Pain is a clinical discomfort that lasts more than 3 months post-surgery without other causes of pain such as chronic infection or pain from a chronic condition preceding the surgery This condition negatively impacts health related quality of life and is associated with significant financial burden both for the patient and health care system Patients undergoing a multitude of procedures from amputation to hernia repair are prone to develop CPSP with variable incidences
CPSP may be a result of peripheral and central sensitization triggered by the release of cytokines and chemokines following surgery due to possible alterations in genetic expression At the cellular level after surgical incision tissue cells from local areas have been implicated to drive synthesis of such cytokineschemokines leading to alterations of their serum levels including nerve growth factors NGF and interleukins IL-1β Specific regulatory mechanisms leading to augmented synthesis of these cytokines in the context of CPSP remain elusive Several regulatory mechanisms may influence production of each cytokine One method is via epigenetic mechanisms which are defined as the alteration of gene expression without any structural genomic alterations that may regulate cytokine production at the transcriptional and post transcriptional levels Among these listed epigenetic mechanisms DNA methylation has been well studied and plays a key role in translation4 In general hypomethylation of the promoter region leads to increased gene expression and vice versa In this study the investigators wish to investigate how these mechanisms could be implicated in the expression of cytokines and chemokines in CPSP
Patients undergoing unilateral thoracotomy will be included in this study Their surgery and follow up care will proceed according to standard of care guidelines Thoracic epidural analgesia or patient controlled analgesia PCA pumps will be offered to each study participant as per standard of care Patients pain will be assessed preoperatively and postoperatively on day 1 and 3 months Blood samples will also be taken during these times points and analyzed to determined the concentrations of the following cytokines chemokines and growth factorsepidermal growth factor eotaxin fibroblast growth factor basic G-CSF GM-CSF human growth factor IFN-α IFN-γ IL-1ra IL-1β IL-2 IL-2r IL-4 IL-5 IL-6 IL-7 IL-8 IL-10 IL-12 p40p70 IL-13 IL-15 IL-17 IP-10 MCP-1 MIG MIP-1α MIP-1β RANTES TNF-α and VEGF The occurrence of DNA methylation at the promotor region of these targets will be assessed via polymerase chain reaction PCR analysis Results of these postoperative analyses will be compared to pre-operative molecular concentrations and pain scores to determine the association between epigenetic modifications if any and the development of CPSP and whether these modifications are driven by DNA promotor methylation
CPSP may be a result of peripheral and central sensitization triggered by the release of cytokines and chemokines following surgery due to possible alterations in genetic expression At the cellular level after surgical incision tissue cells from local areas have been implicated to drive synthesis of such cytokineschemokines leading to alterations of their serum levels including nerve growth factors NGF and interleukins IL-1β Specific regulatory mechanisms leading to augmented synthesis of these cytokines in the context of CPSP remain elusive Several regulatory mechanisms may influence production of each cytokine One method is via epigenetic mechanisms which are defined as the alteration of gene expression without any structural genomic alterations that may regulate cytokine production at the transcriptional and post transcriptional levels Among these listed epigenetic mechanisms DNA methylation has been well studied and plays a key role in translation4 In general hypomethylation of the promoter region leads to increased gene expression and vice versa In this study the investigators wish to investigate how these mechanisms could be implicated in the expression of cytokines and chemokines in CPSP
Patients undergoing unilateral thoracotomy will be included in this study Their surgery and follow up care will proceed according to standard of care guidelines Thoracic epidural analgesia or patient controlled analgesia PCA pumps will be offered to each study participant as per standard of care Patients pain will be assessed preoperatively and postoperatively on day 1 and 3 months Blood samples will also be taken during these times points and analyzed to determined the concentrations of the following cytokines chemokines and growth factorsepidermal growth factor eotaxin fibroblast growth factor basic G-CSF GM-CSF human growth factor IFN-α IFN-γ IL-1ra IL-1β IL-2 IL-2r IL-4 IL-5 IL-6 IL-7 IL-8 IL-10 IL-12 p40p70 IL-13 IL-15 IL-17 IP-10 MCP-1 MIG MIP-1α MIP-1β RANTES TNF-α and VEGF The occurrence of DNA methylation at the promotor region of these targets will be assessed via polymerase chain reaction PCR analysis Results of these postoperative analyses will be compared to pre-operative molecular concentrations and pain scores to determine the association between epigenetic modifications if any and the development of CPSP and whether these modifications are driven by DNA promotor methylation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None