The Effects of Metformin on Morbidity and Mortality in Elderly Patients (MET-ELD)

The Effects of Metformin on Morbidity and Mortality in Elderly Patients- a Prospective Randomized Control Trial (RCT)

Elderly patients have an increased susceptibility to burns and a substantial mortality that has not significantly changed over the last three decades. Elderly burn patients not only have an augmented response to burn but also express a prolonged hypermetabolic response.Glucose metabolism with insulin resistance is a hypermetabolic response pathway that profoundly affects post-burn outcomes. The aim if this study is to determine whether metformin can improve morbidity and mortality in elderly burn patients. The investigators hypothesize that metformin will improve clinical outcomes and mortality of elderly burn patients by alleviating the complex inflammatory and hypermetabolic responses after burn.

Study Overview

• Status: Not yet recruiting
• Conditions: Burns
• Intervention / Treatment: Drug: Placebos; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marc G Jeschke, MD PhD; Phone Number: 40694 905-521-2100; Email: marc.jeschke@hhsc.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences Centre
      • Principal Investigator: Marc G. Jeschke, MD PhD
      • Contact: Marc G. Jeschke, MD PhD; Phone Number: 40694 905-521-2100; Email: marc.jeschke@hhsc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 60 - 99 years of age.
2. ≥5% total body surface area (TBSA) burn.
3. Admitted to burn center ≤ 120 hours post-burn injury.
4. At least one surgical intervention likely required.
5. Provide written informed consent.

Exclusion Criteria:

1. Death upon admission.
2. Decision not to treat due to burn injury severity.
3. Presence of anoxic brain injury that is not expected to result in complete recovery.
4. Pre-existing renal failure (eGFR is < 30 mL/min).
5. Severe liver disease (Child-Pugh C).
6. Pre-existing insulin-dependent type II diabetes.
7. Clinical contraindication to give metformin.
8. Allergy to metformin or insulin.
9. History of lactic acidosis while receiving metformin treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Drug: Placebos; Placebo twice a day, administered orally or via gastric tube.
Experimental: Metformin	Drug: Metformin; Metformin 500 mg twice a day, administered orally or via gastric tube.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Record mortality	Patient mortality will be recorded during hospitalization and outpatient follow-ups.	Acute hospitalization up to one year post burn.
Record the episodes of sepsis.	Patients will be assessed daily for episodes of sepsis. The total number of episodes over the course of hospital stay will be recorded.	daily until discharge (1-4 months post admission depending on severity of injury)]
Record episodes of infection.	Patients will be assessed daily for episodes of infection. The total number of episodes over the course of hospital stay will be recorded.	daily until discharge (1-4 months post admission depending on severity of injury)]
Record episodes of pneumonia.	Patients will be assessed daily for episodes of infection. The total number of episodes over the course of hospital stay will be recorded.	daily until discharge (1-4 months post admission depending on severity of injury)]
Organ function - Bilirubin	Organ function will be assessed by measuring the biomarker: bilirubin (umol).	twice weekly until discharge (1-4 months post admission depending on severity of injury)]
Organ function - Creatinine	Organ function will be assessed by measuring the biomarker: creatinine (umol/L).	twice weekly until discharge (1-4 months post admission depending on severity of injury)]
Organ function - Alkaline phosphatase (ALP)	Organ function will be assessed by measuring the biomarker: ALP (U/L).	twice weekly until discharge (1-4 months post admission depending on severity of injury)]
Organ function - Alanine transaminase (ALT)	Organ function will be assessed by measuring the biomarker: ALT (U/L).	twice weekly until discharge (1-4 months post admission depending on severity of injury)]
Organ function - Blood Urea Nitrogen (BUN)	Organ function will be assessed by measuring the biomarker: BUN (mmol).	twice weekly until discharge (1-4 months post admission depending on severity of injury)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of steady-state resting energy expenditure (REE)	Metabolic response to injury and illness can be studied by measuring steady-state resting energy expenditure. Hypermetabolism is used as a secondary endpoint as stress-induced diabetes is associated with inflammation and hypermetabolism.	weekly until discharge if a patient is intubated and ventilated (1-4 months post admission depending on severity of injury)]
Perform oral glucose tolerance test	Standard fasting oral glucose tolerance test with an intake of 75 g of glucose. Subsequent measurements (in mg/dl) of glucose in blood, insulin and c-peptide will be conducted over 2 hours.	once at discharge from hospital (1-4 months post admission depending on the severity of injury)]

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Marc G Jeschke, MD PhD, Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: July 28, 2020
• First Submitted That Met QC Criteria: August 26, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 15230

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes