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DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Traumatic Brain Injury

This study has been completed.
Sponsor:
Collaborators:
Vanderbilt Institute for Clinical and Translational Research (CTSA)
Eastern Association for the Surgery of Trauma (EAST)
Information provided by (Responsible Party):
Mayur Patel, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01322048
First received: March 2, 2011
Last updated: June 12, 2017
Last verified: June 2017
  Purpose

The investigators intend to determine the effect of adrenergic blockade on 1) short-term physiology, behavior, and cognition and 2) long-term neuropsychological outcomes after severe Traumatic Brain Injury (TBI).

The primary hypothesis is that adrenergic blockade after severe TBI will be associated with increased ventilator-free days.


Condition Intervention Phase
Brain Injuries Craniocerebral Trauma Trauma, Nervous System Traumatic Brain Injury Drug: IV Propranolol and Per Tube Clonidine Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Severe Traumatic Brain Injury, A Pilot Randomized Clinical Trial Using Propranolol and Clonidine

Resource links provided by NLM:


Further study details as provided by Mayur Patel, Vanderbilt University:

Primary Outcome Measures:
  • Ventilator-free Days [ Time Frame: Baseline to day 28 ]

Secondary Outcome Measures:
  • Plasma Norepinephrine Levels [ Time Frame: Post-treatment (t=Day 8) ]

Enrollment: 48
Study Start Date: August 2011
Study Completion Date: December 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Adrenergic Blockade
Propranolol and Clonidine
Drug: IV Propranolol and Per Tube Clonidine
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo IV q6h and Per Tube q12, both for 7 days

Detailed Description:

Severe traumatic brain injury (TBI) is associated with sympathetic hyperactivity resulting in catecholamine excess, abnormal heart rate variability, agitation and sympathetic storms, deep white matter changes, and poor neuropsychological outcomes. Notably, persistent sympathetic hyperactivity after TBI results in higher days of mechanical ventilation and longer intensive care unit (ICU) length of stay (LOS). While there are data describing limited portions of this response, the full spectrum of sympathetic hyperactivity after severe TBI has not been systemically described or methodically intervened upon.

We will perform a double-blinded, randomized, placebo-controlled pilot trial in a 100 patient cohort in which one group will receive centrally acting sympatholytic drugs, propranolol and clonidine, and the other group, placebo, within 48 hours of severe TBI. The length of therapy will be 7 days.

The primary question studied is whether ventilator-free days will be increased after therapy.

Secondary endpoints include plasma and urine catecholamine levels, heart rate and blood pressure variability, responses to autonomic cold pressor testing, assessments of coma, sedation, and agitation, sedative requirements, analgesic use, antipsychotic medication use, coma-free days, ventilator-free days, Intensive Care Unit (ICU) length of stay, and survival. Also, neuropsychological outcomes will be measured at ICU discharge, 3 months, and 12 months.

Interim Analysis: At approximately 50% targeted accrual, n=46 randomized subjects, an interim analysis will be performed with A Priori (planned) futility and efficacy rules, which are DSMB and IRB approved.

  Eligibility

Ages Eligible for Study:   16 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: 16 years to 64 years
  • Glasgow Coma Scale score less than or equal to 8 (Severe TBI) with injury on CT
  • Screen within 24 hours of injury

Exclusion Criteria:

  • Pre-existing heart disease (i.e. coronary heart disease)
  • Pre-existing cardiac dysrhythmia
  • Allergy to study drugs
  • Penetrating brain injury
  • Pre-existing brain dysfunction (i.e. prior severe TBI, debilitating stroke)
  • Impending brain herniation (i.e. loss of bilateral corneal reflexes)
  • Craniectomy or craniotomy
  • Spinal cord injury
  • Myocardial injury
  • Severe liver disease
  • Current use of beta-blockers and/or alpha-2-agonist
  • Withdrawal of care expected in 24 hours
  • Prisoners
  • Pregnant women
  • Unable to follow-up through final visit
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01322048

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt University
Vanderbilt Institute for Clinical and Translational Research (CTSA)
Eastern Association for the Surgery of Trauma (EAST)
Investigators
Principal Investigator: Mayur B Patel, MD, MPH Vanderbilt University Medical Center
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mayur Patel, Assistant Professor of Surgery and Neurosurgery, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01322048     History of Changes
Other Study ID Numbers: 110429
Study First Received: March 2, 2011
Results First Received: April 18, 2017
Last Updated: June 12, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mayur Patel, Vanderbilt University:
Sympathetic Hyperactivity
Traumatic Brain Injury
Agitation
Severe TBI
TBI
Catecholamines
Heart rate variability
Adrenergic alpha-Agonists
Adrenergic beta-Antagonists
Cognitive Impairment

Additional relevant MeSH terms:
Brain Injuries
Wounds and Injuries
Hyperkinesis
Craniocerebral Trauma
Trauma, Nervous System
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dyskinesias
Neurologic Manifestations
Signs and Symptoms
Propranolol
Clonidine
Adrenergic Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on July 19, 2017