Application of High-dose Insulin Therapy to Improve Liver Function and Regeneration

NCT06126419 | Recruiting DMC

• 1 other identifier: 2023-8880
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this interventional study is determine if the future liver remnant can be optimized by improving liver function pre-operatively in patients who are scheduled for major hepatectomy. The main questions it aims to answer are:

1. 1.Does high-dose insulin therapy improve liver function in the pre-operative setting?
2. 2.What is the effect of high-dose insulin therapy on liver function and liver regeneration after a liver venous deprivation (LVD) procedure?
3. 3.What is the relationship between volume hypertrophy and function in the regenerating liver? Participants will receive a 6-hour infusion of insulin and dextrose to maintain a hyperinsulinemic-normoglycemic state in the weeks prior to planned liver surgery to assess its effect on liver function measured by 99m-Tc-Mebrofenin hepatobiliary scintigraphy.

Conditions

Liver Dysfunction; Liver Metastasis Colon Cancer; Liver Regeneration

Keywords

Hyperinsulinemic-Normoglycemic Clamp; High Dose Insulin Therapy; 99mTc-Mebrofenin Hepatobiliary Scintigraphy; Colorectal Cancer Liver Metastasis; Liver Resection

Outcome Measures

Primary Outcomes (3)

• Liver function improvement after high-dose insulin therapy measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS).

  99mTc-Mebrofenin HBS is a diagnostic nuclear medicine imaging procedure used to evaluate liver function by measuring radiotracer uptake and excretion. The outcome will be evaluating a measurable increase in 99mTc-Mebrofenin (measured %/min/meter\^2) from baseline scan to post-treatment scan.

  Baseline to 24-hours post treatment

• Liver function improvement after high-dose insulin therapy after LVD measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS).

  99mTc-Mebrofenin HBS is a diagnostic nuclear medicine imaging procedure used to evaluate liver function by measuring radiotracer uptake and excretion. The outcome will be evaluating a measurable increase in 99mTc-Mebrofenin (measured %/min/meter\^2) from baseline scan to post-treatment scan.

  Baseline to 7 days post treatment

• Liver regeneration improvement after high-dose insulin therapy after LVD measured CT volumetry

  The volume of the liver can be measured from liver protocoled CT scans

  Baseline to 7 days post treatment

Study Arms (3)

Group 1: Effect of high-dose insulin therapy on pre-operative liver function

EXPERIMENTAL

Group 1 will consist of participants scheduled for liver resection and will undergo high-dose insulin pre-operatively to determine if baseline liver function can be optimized/improved, as measured by 99mTc-Mebrofenin HBS.

Drug: High-Dose Insulin Therapy

Group 2: Effect of high-dose insulin therapy on pre-operative liver function after LVD

EXPERIMENTAL

Group 2 will consist of participants scheduled for liver resection that require LVD. The participants in the experimental arm will receive high-dose insulin therapy after LVD.

Drug: High-Dose Insulin Therapy

Group 3: Effect of high-dose insulin therapy on pre-operative liver function after LVD

NO INTERVENTION

Group 3 will consist of participants scheduled for liver resection that require LVD. The participants in the no intervention arm will not undergo intervention with high-dose insulin therapy after LVD.

Interventions

High-Dose Insulin Therapy DRUG

A baseline blood glucose value will be obtained. Two units of insulin will be administered IV if the blood glucose is \> mmol/L. An insulin infusion of 0.12 units/kg/hr will be started. Ten minutes after starting the insulin, and when the blood glucose is \< 6 mmol/L, dextrose 20% supplemented with phosphate (30 mmol/L) will be infused. Blood glucose levels will be measured every 15 minutes, and the dextrose infusion rate adjusted to maintain glycemic levels between 4 and 6 mmol/L for a duration of 6 hours. At the end of the 6 hour period, the insulin will be stopped and the dextrose will be weaned off.

Group 1: Effect of high-dose insulin therapy on pre-operative liver function; Group 2: Effect of high-dose insulin therapy on pre-operative liver function after LVD

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 old
• Candidate for major liver resection
• Resectable colorectal liver metastasis

You may not qualify if:

• Inability to give consent
• Type 1 diabetes mellitus
• Uncontrolled blood glucose levels (fasting level \> 10 mmol/L)
• Unresectable colorectal liver metastasis
• Extrahepatic metastatic disease that is unresectable

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill Univeristy Health Centre

Montreal, Quebec, H3A 1A1, Canada

RECRUITING

MeSH Terms

Conditions

Liver Diseases

Condition Hierarchy (Ancestors)

Digestive System Diseases

Central Study Contacts

Jennifer Kalil, MD

CONTACT

514-934-1934; jennifer.kalil@mail.mcgill.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery, Program Leader - MUHC-RI Cancer Research Program

Model Details: Group 1 will consist of participants scheduled for liver resection and will undergo high-dose insulin therapy preoperatively to determine if baseline liver function can be optimized/improved, as measured by 99mTc-Mebrofenin HBS. Cytokine profiling will also be collected and analyzed pre- and post-insulin infusion. Group 2 will consist of participants scheduled for liver resection that require LVD. They will then be randomized to two different arms -- control vs high-dose insulin therapy.

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: November 13, 2023
• Study Start: November 8, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 20, 2024

Record last verified: 2024-11

Locations

CA (1)