Reducing Inflammatory Syndrome in Surgery - Colorectal (RISIS-CR) Trial

NCT06646809 | Recruiting Phase 3

• 1 other identifier: 2022/00724
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

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.

Conditions

Colorectal Cancer

Keywords

Geroprotector; Alpha-ketoglutarate

Outcome Measures

Primary Outcomes (1)

• Comparison of postoperative CRP levels between the low inflammatory responders, high inflammatory responders with AKG and high inflammatory responders with placebo

  Comparison of postoperative CRP levels between the groups.

  Postoperative till day 30

Secondary Outcomes (1)

• Compare changes in frailty, cognition, recovery trajectory, clinical outcomes, and surgical complications

  Postoperative till day 30

Study Arms (3)

Low inflammatory responder

OTHER

Low inflammatory responder group - to receive standard care

Other: Standard care

High inflammatory responder - AKG

EXPERIMENTAL

High inflammatory responder group - to receive AKG tablets (1g a day, once a day, taken orally)

Dietary Supplement: Alpha-ketoglutarate

High inflammatory responder - placebo

PLACEBO COMPARATOR

High inflammatory responder group - to receive placebo tablets (1g a day, once a day, taken orally)

Dietary Supplement: Placebo

Interventions

Alpha-ketoglutarate DIETARY_SUPPLEMENT

Alpha-ketoglutarate supplements

High inflammatory responder - AKG

Placebo DIETARY_SUPPLEMENT

Placebo tablets

High inflammatory responder - placebo

Standard care OTHER

Standard care

Low inflammatory responder

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged at least 45 years old
• Undergoing elective colorectal cancer surgery
• Able to give informed consent

You may not qualify if:

• Undergoing emergency colorectal cancer surgery
• Unable to give informed consent
• Females who are pregnant
• Cognitively impaired patients

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National Medical Research Council (NMRC), Singapore: collaborator

Study Sites (4)

National University Hospital

Singapore, Singapore, 119074, Singapore

RECRUITING

Ng Teng Fong General Hospital

Singapore, Singapore

RECRUITING

Sengkang General Hospital

Singapore, Singapore

RECRUITING

Singapore General Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Ketoglutaric Acids; Standard of Care

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Glutarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Keto Acids; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Lian Kah Ti

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lian Kah Ti

CONTACT

6567724200; anatilk@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 groups of patients - low inflammatory responder, high inflammatory responder with AKG, high inflammatory responder with placebo

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: October 17, 2024
• Study Start: May 9, 2024
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 17, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

SG (4)