Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial

NCT02746432 | Unknown Phase 4 DMC

• 1 other identifier: KSULDRCCRCMH001
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

Research Problem: Surgical stress induces inflammation and postoperative immuno-suppression, which are risk. factors for both post-operative complication and possible disease recurrence. Colorectal cancer is in the top 5 malignancies in the Kingdome and the highest incidence in males. Recurrent disease locally or distally occurs in 35% of patients and is the leading cause of death in these patients. Despite the new era of laparoscopic surgery, still surgical stress is present and equally traumatic to the conventional open colorectal resection, earlier studies showed no major differences in post-operative inflammatory and immunological reactions. The previous studies revealed the anti-inflammatory effects of the hyper-insulinimic euglycemic therapy. Benefits observed in both major liver resection and in cardiac surgery. The anti-inflammatory effect reduced the surgical stress and postoperative inflammation. The hypothesis is "Can intraoperative hyper-insulinimic euglycemic infusion reduce post operative inflammation and immunomodulation in colon cancer patients undergoing a curative surgery?" Research methodology Triple blinded randomized controlled study with estimated sample size of 144 patients of non-metastatic colorectal cancer patients operated at King Saud University Medical city with a confirmed diagnosis of colon adenocarcinoma. Patients Consented will undergo computer randomization to receive intraoperative hyper-insulinimic normoglycemic infusion (experimental) or standardized insulin sliding scale and saline (control). A common preoperative and postoperative pathway with standardized management and pain control in both groups. Outcomes will be measured via a battery of laboratory test consist of routine labs, inflammatory markers and immunological markers to be repeated at fixed timed intervals. All patients will be followed by regularly for 5 years. Research objectives Primary outcomes to examine:

• The anti-inflammatory effects of intraoperative hyper-insulinimic euglycemic therapy in patients undergoing colorectal cancer surgery.
• The immunomodulatory effect of intraoperative hyper-insulinimic euglycemic infusion Secondary outcomes:
• Thirty days post-operative morbidity.
• Overall survival rate.
• Disease-free survival rate.

Conditions

Colon Cancer

Keywords

CRC-Insulin

Outcome Measures

Primary Outcomes (1)

• The anti-inflammatory effects of intraoperative hyper-insulinimic euglycemic therapy in patients undergoing colorectal cancer surgery.

  effect on Inflamatory profile namely levels of Tnf- Alpha , IL-8 , IL-6 , IL-10 , IL-1B,IL-18 , IFNγ, MIp1-Alpha , MMP-8 , TGF Beta , CRP

  1 month

Secondary Outcomes (1)

• The immunomodulatory effect of intraoperative hyper-insulinimic euglycemic infusion.

  1 month

Other Outcomes (4)

• Thirty days post-operative morbidity

  30 days

• Overall survival rate

  5 years

• Disease-free survival rate

  5 years

Study Arms (2)

Control group

NO INTERVENTION

Routine intra operative saline infusion to be administered.pre-operation and timed assessment lab set to be obtained.

Intervention group.Hyper insulinemic euglycemic clamp

EXPERIMENTAL

After obtaining a baseline preoperative lab set blood glucose value, 2 U/kg bolus of insulin to be administered IV followed by an infusion of 2 U/ kg/min.fiver - Ten minutes after starting the insulin (Human regular insulin) ) infusion, and when the blood glucose is \<6.1 mmol /L (110 mg /dL). an Infusion of dextrose 20% supplemented with pottasium phosphate (30 mmol/L ) to be administered. In the operating room, blood glucose levels were measured every 5-15 minutes, and the dextrose infusion rate was adjusted to maintain arterial glycemia between 3.5 and 6.1 mmol/L (63-110 mg/dL). timed intra operative lab assessment to be obtained.

Drug: Hyper insulinemic euglycemic clamp

Interventions

Hyper insulinemic euglycemic clamp DRUG

After obtaining a baseline preoperative lab set blood glucose value, 2 U/kg bolus of insulin (Human regular insulin) to be administered IV followed by an infusion of 2 U/ kg/min.fiver - Ten minutes after starting the insulin infusion, and when the blood glucose is \<6.1 mmol /L (110 mg /dL). an Infusion of dextrose 20% supplemented with pottasium phosphate (30 mmol/L ) to be administered. In the operating room, blood glucose levels were measured every 5-15 minutes, and the dextrose infusion rate was adjusted to maintain arterial glycemia between 3.5 and 6.1 mmol/L (63-110 mg/dL). timed intra operative lab assessment to be obtained.

Intervention group.Hyper insulinemic euglycemic clamp

Eligibility Criteria

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

You may qualify if:

• Age \> 18 years
• Documented CRC by histopathology

You may not qualify if:

• Patient not consenting to the study or refused.
• Metastatic disease at the time of diagnosis.
• Contraindications to insulin
• Pregnancy

Sponsors & Collaborators

• King Saud University: lead

Study Sites (1)

King Saud University Medical City

Riyadh, 7805, Saudi Arabia

Location

Related Publications (15)

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  PMID: 37526194 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Faisal A Al-Alem, MBBS SBGS

CONTACT

00966506238992; faisal.alalem@gmail.com

Mazen M Hassanain, MBBS FRCSC FACS PhD

CONTACT

+966 50 514 1090; mhassanain@ksu.edu.sa

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor & Counsultant HPB and transplant Surgeon

Study Record Dates

• First Submitted: April 6, 2016
• First Posted: April 21, 2016
• Study Start: January 1, 2018
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

SA (1)