Propranolol for the Treatment of Traumatic Brain Injury

NCT06262061 | Not Yet Recruiting Early Phase 1

• 1 other identifier: PRO-TBI-FS
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Traumatic brain injury (TBI) is a leading cause of global disease and directly affects over 1.5 million Canadians, with 165 000 TBIs occurring yearly in Canada. Despite the burden of TBIs, there are limited treatment options available and current treatments generally focus on supportive care. The aim of TBI treatment is reduce inflammation and damage occurring after the TBI (secondary injury). Beta- blockers (BBs) are medications commonly used to block the actions of endogenous catecholamines- hormones that are thought to contribute to secondary injury within brain tissue. This reduces metabolic demand in the vulnerable, injured brain. BBs have been studied in several retrospective trials and one single-center, non- blinded randomized controlled study. These results point towards a benefit to the use of BBs in TBI but need to be confirmed in a rigorous manner before they are widely adopted. The current study aims to assess the feasibility of a single centre randomized controlled trial of BBs versus placebo to treat moderate to severe TBI. This feasibility trial will inform the planning of a large multi-center study powered to detect a difference in cognitive outcomes and mortality. It also will allow the investigators to gather biologic samples for measuring serum catecholamines and inflammatory mediators to better understand the basic science mechanisms of BBs in this patient population; and to assess the feasibility of using the Cambridge Battery to assess cognitive outcomes of trial participants.

Conditions

TBI (Traumatic Brain Injury)

Keywords

Beta-blockers; TBI; Trauma

Outcome Measures

Primary Outcomes (2)

• Hospital Mortality

  1 month

• Cognitive function

  Assessment of neurological function at time of discharge, 2 week follow-up, and 6 month follow-up using Glascow Outcome Scale Extended (GOS-E) and Cambridge Battery via a validated online platform

  6 months

Secondary Outcomes (1)

• Catecholamines/Inflammatory markers

  patient's blood will be drawn to measure the 5 serum biomarkers on admission and then at 24hr, 48hrs, 72 hours and 5 days following the initial TBI injury

Study Arms (2)

Propranolol Group

ACTIVE COMPARATOR

The propranolol group will receive 20mg of oral propranolol twice daily for 14 days (or until hospital discharge or death).

Drug: Propranolol

Control Group

PLACEBO COMPARATOR

Control group will receive an oral placebo.

Drug: Placebo

Interventions

Propranolol DRUG

20mg oral propranolol BID x 14 days

Propranolol Group

Placebo DRUG

Placebo pill orally BID x 14 days

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (\>18/= 18 years of age) who have sustained a TBI
• Initial GCS during the first 6 hours of assessment of 5- 12 (inclusive)

You may not qualify if:

• Home beta- blocker therapy
• New indication for beta- blocker therapy during hospital stay
• Contraindication to beta- blocker therapy
• Allergy
• Severe asthma/ COPD
• Sinus bradycardia and greater than first degree block
• Patients in cardiogenic shock
• Right ventricular failure secondary to pulmonary hypertension
• Congestive heart failure unless the failure is secondary to a tachyarrhythmia treatable with propranolol
• Patients requiring any vasoactive medications to maintain their blood pressure at the time of enrollment
• Patients requiring or are on any of the following medications:
• Digitalis
• Anesthetic agents that maintain cardiac contractility by virtue of their effect on catecholamine release (e.g., ether)
• Epinephrine, noradrenaline, adrenaline, and isoproterenol
• Antiarrhythmic cardiac depressant drugs such as procainamide or quinidine

Sponsors & Collaborators

• London Health Sciences Centre: lead

MeSH Terms

Conditions

Brain Injuries, Traumatic; Wounds and Injuries

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Central Study Contacts

Mohammad Hmidan Simsam

CONTACT

5196397499; mhmidansimsam2024@meds.uwo.ca

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized in a 1:1 allocation to either the propranolol or control group. Our hospital pharmacy will control the randomization procedure. The propranolol group will receive over-encapsulated whole marketed tablets comprised of 20mg oral propranolol \[USP grade\] filled with lactose monohydrate powder \[NF grade\] encapsulated with opaque gelatin capsules twice daily for 14 days (or until hospital discharge or death). The control group will receive an oral placebo comprised of lactose monohydrate powder \[NF grade\] encapsulated with indistinguishable opaque gelatin capsules. The pharmacy will have access to the randomization key. Nursing staff will remove the gelatin capsule casing and dissolve the trial drug \& placebo in sterile water prior to administering it enterally via a feeding tube to the participants. Aside from the nursing staff, the participants, research team, and remainder of the clinical care teams will all remain blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Medicine

Model Details: Prospective, single- center double- blinded randomized control trial comparing placebo to propranolol for the treatment of moderate- severe traumatic brain injury.

Study Record Dates

• First Submitted: September 21, 2023
• First Posted: February 15, 2024
• Study Start: March 1, 2024
• Primary Completion: April 1, 2025
• Study Completion: September 1, 2025
• Last Updated: February 15, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share