Catecholamine Blockade Post-burn

Clinical and Molecular Effects of Catecholamine Blockade Post-burn

Severe burn is associated with a wide array of stress, metabolic, and physiologic processes in an attempt to restore homeostasis. The catecholamine induced stress response following severe burns is particularly exaggerated and manifests detrimentally as inflammation, insulin resistance, hypermetabolism, and associated profound protein catabolism. The investigators hypothesize that catecholamine blockade will lead to restored IR signaling and result in improved post-burn morbidity. The investigators will further determine the molecular mechanisms mediating these effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Burns
• Intervention / Treatment: Drug: placebo; Drug: propranolol

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Ross Tilley Burn Centre - Sunnybrook HSC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients between 18 and 90 years of age
• >25% TBSA burn

Exclusion Criteria:

• Death upon admission
• Decision not to treat due to burn injury severity

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Control	Drug: placebo; identically packed placebo
EXPERIMENTAL: Beta blockade	Drug: propranolol; 20-40 mg q6-8h

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Conduct at week 1 post admission
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.	Conduct at week 3 post admission
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.	Conduct at discharge (1-4 months post admission depending on severity of injury)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure concentrations of serum cytokines	Inflammatory response will be assessed by measuring the concentrations (pg/ml) of a panel of serum cytokines (IL-1, IFN, TNF etc.) using the Bio-Plex 17-Plex Suspension assay.	weekly until discharge (1-4 months post admission depending on severity)
Record the episodes of Pneumonia	Pneumonia is defined by the following criteria: new progressive and persistent infiltrate, consolidation, or cavitations, in light of the baseline evaluation for inhalational injury on chest X-ray, along with signs of sepsis, worsening gas exchange (decreased P/F ratio), increased O2, and change in the sputum, e.g. purulent or increased sputum production.	daily until discharge (1-4 months post admission depending on severity)
Record the episodes of sepsis	Patients are evaluated daily and the number of episodes of sepsis or bloodstream infection will be recorded	daily until discharge (1-4 months post admission depending on severity of injury)
Measure the levels of activated signaling proteins using protein blotting	The level of activation of a protein signaling cascade (fold change compared to control), as indicated by the amount of phosphorylated protein substrates (e.g. p-Akt/Akt), will be measured in tissue obtained at operation using protein blotting techniques in the laboratory.	assess at 1st operation (week 1-2 post admission on average) and 3rd operation (week 3-4 post admission on average)

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: January 24, 2011
• First Submitted That Met QC Criteria: February 17, 2011
• First Posted (ESTIMATE): February 18, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: Propran_Jeschke