Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06646809
Status:
RECRUITING
Last Update Posted:
None
First Post:
2023-07-24
Brief Title:
Reducing Inflammatory Syndrome in Surgery - Colorectal RISIS-CR Trial
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Reducing Inflammatory Syndrome in Surgery - Colorectal RISIS-CR Trial
Status:
RECRUITING
Status Verified Date:
2024-08
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:
RISIS-CR
Brief Summary:
The study proposes to identify inflammatory responsiveness of patients prior to CRC surgery and administer prophylactic anti-inflammatory treatment targeted only to those with an excessive pro-inflammatory response The study team believe this to be a creative approach as the principles of personalized medicine will be used to treat the appropriate patients and equally as importantly to not further suppress the inflammatory response of those who have poor immune function already
Geroprotectors reduce inflammation and may reduce postoperative SIR and complications after CRC surgery In this proposal we intend to use alpha ketoglutarate AKG a geroprotector supplement that enjoys a GRAS generally regarded as safe status with the FDA 12 Apart from reducing inflammation and inhibiting the mTOR pathway AKG also prevents loss of muscle mass improves brain oxygenation has cardioprotective effects and improves renal function It also has anti-cancer effects beyond mTOR pathway inhibition including regulating HIF-1 activity suppressing secretion of angiogenic factors and regulating epigenetic processes
Geroprotectors reduce inflammation and may reduce postoperative SIR and complications after CRC surgery In this proposal we intend to use alpha ketoglutarate AKG a geroprotector supplement that enjoys a GRAS generally regarded as safe status with the FDA 12 Apart from reducing inflammation and inhibiting the mTOR pathway AKG also prevents loss of muscle mass improves brain oxygenation has cardioprotective effects and improves renal function It also has anti-cancer effects beyond mTOR pathway inhibition including regulating HIF-1 activity suppressing secretion of angiogenic factors and regulating epigenetic processes
Detailed Description:
The incidence of colorectal cancer CRC increases exponentially with age with 50 of CRC first diagnosed at 50 years or older Surgery is the mainstay of treatment However older patients are more likely to develop postoperative ileus and anastomotic leak longer hospital stays and higher mortality In the long-term they are more likely to experience fatigue and slow recovery
Surgery triggers an inflammatory response In some cases the immune system is unable to distinguish between the stimuli of major surgery ideally a modest response and trauma or infection This overshoot manifests as a postoperative systemic inflammatory response SIR and may lead to tissue destruction and organ dysfunction In CRC surgery SIR as defined by C-reactive protein CRP elevation is associated with postoperative Clavien-Dindo grades III and IV complications where intervention is needed These complications include infection and anastomotic leak and are linked to reduced overall survival independent of both surgery-related complications and tumour stage In addition preoperative systemic inflammation is a marker of poor prognosis As ageing is often accompanied by a chronic low-grade inflammation it was not surprising that preoperative systemic inflammation is more common in older patients
The use of anti-inflammatory drugs to reduce SIR has had mixed successes Chronic steroid use is a recognized risk factor for anastomotic leak but in a recent meta-analysis the use of preoperative corticosteroids lowered markers of SIR and reduced postoperative infective complications Similarly although NSAIDs have been shown to reduce hospital stay and hasten recovery in bowel function a recent meta-analysis indicated that it increases the risk of anastomotic leaks
Older patients may have impaired immune response to surgical stress from immunosenescence but conversely some may develop a more intense and prolonged response In a population study of elderly people this heterogeneity conferred a survival benefit to those who could mount a pro-inflammatory response whereas those with poor pro-inflammatory response were more prone to infections Therefore suppressing the postoperative SIR in pro-inflammatory patients is likely beneficial but not in patients with low pro-inflammatory potential
Surgery triggers an inflammatory response In some cases the immune system is unable to distinguish between the stimuli of major surgery ideally a modest response and trauma or infection This overshoot manifests as a postoperative systemic inflammatory response SIR and may lead to tissue destruction and organ dysfunction In CRC surgery SIR as defined by C-reactive protein CRP elevation is associated with postoperative Clavien-Dindo grades III and IV complications where intervention is needed These complications include infection and anastomotic leak and are linked to reduced overall survival independent of both surgery-related complications and tumour stage In addition preoperative systemic inflammation is a marker of poor prognosis As ageing is often accompanied by a chronic low-grade inflammation it was not surprising that preoperative systemic inflammation is more common in older patients
The use of anti-inflammatory drugs to reduce SIR has had mixed successes Chronic steroid use is a recognized risk factor for anastomotic leak but in a recent meta-analysis the use of preoperative corticosteroids lowered markers of SIR and reduced postoperative infective complications Similarly although NSAIDs have been shown to reduce hospital stay and hasten recovery in bowel function a recent meta-analysis indicated that it increases the risk of anastomotic leaks
Older patients may have impaired immune response to surgical stress from immunosenescence but conversely some may develop a more intense and prolonged response In a population study of elderly people this heterogeneity conferred a survival benefit to those who could mount a pro-inflammatory response whereas those with poor pro-inflammatory response were more prone to infections Therefore suppressing the postoperative SIR in pro-inflammatory patients is likely beneficial but not in patients with low pro-inflammatory potential
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