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

Sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06126419

Collaborator

(none)

Enrollment

Arms

19.6

Anticipated Duration (Months)

Study Details

Study Description

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:

Does high-dose insulin therapy improve liver function in the pre-operative setting?
What is the effect of high-dose insulin therapy on liver function and liver regeneration after a liver venous deprivation (LVD) procedure?
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.

Condition or Disease	Intervention/Treatment	Phase
Liver Dysfunction Liver Metastasis Colon Cancer Liver Regeneration	Drug: High-Dose Insulin Therapy	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Application of High-Dose Insulin Therapy Using a Hyperinsulinemic Normoglycemic Clamp to Improve Liver Function and Regeneration

Anticipated Study Start Date :

Nov 13, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Effect of high-dose insulin therapy on pre-operative liver function 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 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.
Experimental: Group 2: Effect of high-dose insulin therapy on pre-operative liver function after LVD 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 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.
No Intervention: Group 3: Effect of high-dose insulin therapy on pre-operative liver function after LVD 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.

Arm

Intervention/Treatment

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

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

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.

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

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

No Intervention: Group 3: Effect of high-dose insulin therapy on pre-operative liver function after LVD

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.

Outcome Measures

Primary Outcome Measures

Liver function improvement after high-dose insulin therapy measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS). [Baseline to 24-hours post treatment]
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.
Liver function improvement after high-dose insulin therapy after LVD measured with 99mTc-Mebrofenin Hepatobiliary Scintigraphy (HBS). [Baseline to 7 days post treatment]
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.
Liver regeneration improvement after high-dose insulin therapy after LVD measured CT volumetry [Baseline to 7 days post treatment]
The volume of the liver can be measured from liver protocoled CT scans

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years old
Candidate for major liver resection
Resectable colorectal liver metastasis

Exclusion Criteria:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

McGill University Health Centre/Research Institute of the McGill University Health Centre

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

peter metrakos, Professor of Surgery, Program Leader - MUHC-RI Cancer Research Program, McGill University Health Centre/Research Institute of the McGill University Health Centre

ClinicalTrials.gov Identifier:

NCT06126419

Other Study ID Numbers:

2023-8880

First Posted:

Nov 13, 2023

Last Update Posted:

Nov 13, 2023

Last Verified:

Nov 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by peter metrakos, Professor of Surgery, Program Leader - MUHC-RI Cancer Research Program, McGill University Health Centre/Research Institute of the McGill University Health Centre

Hyperinsulinemic-Normoglycemic Clamp

High Dose Insulin Therapy

99mTc-Mebrofenin Hepatobiliary Scintigraphy

Colorectal Cancer Liver Metastasis

Liver Resection

Additional relevant MeSH terms:

Neoplasm Metastasis

Liver Diseases

Insulin

Study Results

No Results Posted as of Nov 13, 2023