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

Primary Purpose

Brain Injuries, Craniocerebral Trauma, Trauma, Nervous System

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IV Propranolol and Per Tube Clonidine
Placebo
Sponsored by
Vanderbilt University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Injuries focused on measuring Sympathetic Hyperactivity, Traumatic Brain Injury, Agitation, Severe TBI, TBI, Catecholamines, Heart rate variability, Adrenergic alpha-Agonists, Adrenergic beta-Antagonists, Cognitive Impairment

Eligibility Criteria

16 Years - 64 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Adrenergic Blockade

Placebo

Arm Description

Propranolol and Clonidine

Placebo

Outcomes

Primary Outcome Measures

Ventilator-free Days

Secondary Outcome Measures

Plasma Norepinephrine Levels

Full Information

First Posted
March 2, 2011
Last Updated
July 14, 2017
Sponsor
Vanderbilt University
Collaborators
Vanderbilt Institute for Clinical and Translational Research (CTSA), Eastern Association for the Surgery of Trauma (EAST)
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1. Study Identification

Unique Protocol Identification Number
NCT01322048
Brief Title
DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Traumatic Brain Injury
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
Collaborators
Vanderbilt Institute for Clinical and Translational Research (CTSA), Eastern Association for the Surgery of Trauma (EAST)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Injuries, Craniocerebral Trauma, Trauma, Nervous System, Traumatic Brain Injury
Keywords
Sympathetic Hyperactivity, Traumatic Brain Injury, Agitation, Severe TBI, TBI, Catecholamines, Heart rate variability, Adrenergic alpha-Agonists, Adrenergic beta-Antagonists, Cognitive Impairment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adrenergic Blockade
Arm Type
Experimental
Arm Description
Propranolol and Clonidine
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
IV Propranolol and Per Tube Clonidine
Intervention Description
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo IV q6h and Per Tube q12, both for 7 days
Primary Outcome Measure Information:
Title
Ventilator-free Days
Time Frame
Baseline to day 28
Secondary Outcome Measure Information:
Title
Plasma Norepinephrine Levels
Time Frame
Post-treatment (t=Day 8)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mayur B Patel, MD, MPH
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
23013802
Citation
Patel MB, McKenna JW, Alvarez JM, Sugiura A, Jenkins JM, Guillamondegui OD, Pandharipande PP. Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial. Trials. 2012 Sep 26;13:177. doi: 10.1186/1745-6215-13-177.
Results Reference
derived
Links:
URL
http://www.vanderbilthealth.com/traumasurvivors/36172
Description
Vanderbilt Multidisciplinary Traumatic Brain Injury Clinic (MTBIC)

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

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