Catecholamine Blockade Post-burn

• ClinicalTrials.gov Identifier: NCT01299753
• Recruitment Status: Recruiting
• First Posted: February 18, 2011
• Last Update Posted: April 26, 2017
• Sponsor: Sunnybrook Health Sciences Centre
• Information provided by (Responsible Party): Dr. Marc Jeschke, Sunnybrook Health Sciences Centre

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Burns	Drug: placebo; Drug: propranolol	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Clinical and Molecular Effects of Catecholamine Blockade Post-burn
• Study Start Date: February 2011
• Estimated Primary Completion Date: February 2020
• Estimated Study Completion Date: August 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control	Drug: placebo; identically packed placebo
Experimental: Beta blockade	Drug: propranolol; 20-40 mg q6-8h

Outcome Measures

Primary Outcome Measures :

1. Perform oral glucose tolerance test [ Time Frame: Conduct at week 1 post admission ]
   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.
2. Perform oral glucose tolerance test [ Time Frame: Conduct at week 3 post admission ]
   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.
3. Perform oral glucose tolerance test [ Time Frame: Conduct at discharge (1-4 months post admission depending on severity of injury) ]
   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.

Secondary Outcome Measures :

1. Measure concentrations of serum cytokines [ Time Frame: weekly until discharge (1-4 months post admission depending on severity) ]
   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.
2. Record the episodes of Pneumonia [ Time Frame: daily until discharge (1-4 months post admission depending on severity) ]
   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.
3. Record the episodes of sepsis [ Time Frame: daily until discharge (1-4 months post admission depending on severity of injury) ]
   Patients are evaluated daily and the number of episodes of sepsis or bloodstream infection will be recorded
4. Measure the levels of activated signaling proteins using protein blotting [ Time Frame: assess at 1st operation (week 1-2 post admission on average) and 3rd operation (week 3-4 post admission on average) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Marc G Jeschke, MD PhD; 416-480-6703; marc.jeschke@sunnybrook.ca

Contact: Marjorie A Burnett, HonsBSc; 416-480-6100 ext 88021; marjorie.burnett@sunnybrook.ca

Locations

Canada, Ontario

Ross Tilley Burn Centre - Sunnybrook HSC; Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contact: Marc G Jeschke, MD PhD 416-480-6703 marc.jeschke@sunnybrook.ca

Contact: Marjorie Burnett, Hons.BSc 416-480-6100 ext 88021 marjorie.burnett@sunnybrook.ca

Sub-Investigator: Gordon Rubenfeld, MD

Sponsors and Collaborators

Sunnybrook Health Sciences Centre

Investigators

• Principal Investigator: Marc G Jeschke, MD PhD; Sunnybrook Health Sciences Centre

More Information

• Responsible Party: Dr. Marc Jeschke, Principal Investigator, Sunnybrook Health Sciences Centre
• ClinicalTrials.gov Identifier: NCT01299753 History of Changes
• Other Study ID Numbers: Propran_Jeschke
• First Posted: February 18, 2011
• Last Update Posted: April 26, 2017
• Last Verified: April 2017

Additional relevant MeSH terms:

Burns; Wounds and Injuries; Propranolol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents