Trial Title:
Reducing Inflammatory Syndrome in Surgery - Colorectal (RISIS-CR) Trial
NCT ID:
NCT06646809
Condition:
Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
Geroprotector
Alpha-ketoglutarate
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
3 groups of patients - low inflammatory responder, high inflammatory responder with AKG,
high inflammatory responder with placebo
Primary purpose:
Prevention
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description:
Double-blinded
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Alpha-ketoglutarate
Description:
Alpha-ketoglutarate supplements
Arm group label:
High inflammatory responder - AKG
Intervention type:
Dietary Supplement
Intervention name:
Placebo
Description:
Placebo tablets
Arm group label:
High inflammatory responder - placebo
Intervention type:
Other
Intervention name:
Standard care
Description:
Standard care
Arm group label:
Low inflammatory responder
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients aged at least 45 years old
- Undergoing elective colorectal cancer surgery
- Able to give informed consent
Exclusion Criteria:
- Undergoing emergency colorectal cancer surgery
- Unable to give informed consent
- Females who are pregnant
- Cognitively impaired patients
Gender:
All
Minimum age:
45 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
National University Hospital
Address:
City:
Singapore
Zip:
119074
Country:
Singapore
Status:
Recruiting
Contact:
Last name:
Lian Kah Ti
Email:
anatilk@nus.edu.sg
Contact backup:
Last name:
Ker Kan Tan
Contact backup:
Last name:
Ne-Hooi Will Loh
Contact backup:
Last name:
Chee Kuan Francis Tan
Contact backup:
Last name:
Chunmei Li
Facility:
Name:
Ng Teng Fong General Hospital
Address:
City:
Singapore
Country:
Singapore
Status:
Recruiting
Contact:
Last name:
Wee-Sen Choo
Facility:
Name:
Sengkang General Hospital
Address:
City:
Singapore
Country:
Singapore
Status:
Recruiting
Contact:
Last name:
Frederick Koh
Facility:
Name:
Singapore General Hospital
Address:
City:
Singapore
Country:
Singapore
Status:
Recruiting
Contact:
Last name:
Sophia Tsong Huey Chew
Start date:
May 9, 2024
Completion date:
December 2024
Lead sponsor:
Agency:
National University Hospital, Singapore
Agency class:
Other
Collaborator:
Agency:
National Medical Research Council (NMRC), Singapore
Agency class:
Other
Source:
National University Hospital, Singapore
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06646809
