- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01322048
DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Traumatic Brain Injury
DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Severe Traumatic Brain Injury, A Pilot Randomized Clinical Trial Using Propranolol and Clonidine
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Tennessee
-
Nashville, Tennessee, United States, 37212
- Vanderbilt University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
Placebo IV q6h and Per Tube q12, both for 7 days
|
EXPERIMENTAL: Adrenergic Blockade
Propranolol and Clonidine
|
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Ventilator-free Days
Time Frame: Baseline to day 28
|
Baseline to day 28
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Plasma Norepinephrine Levels
Time Frame: Post-treatment (t=Day 8)
|
Post-treatment (t=Day 8)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mayur B Patel, MD, MPH, Vanderbilt University Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Dyskinesias
- Brain Injuries
- Wounds and Injuries
- Brain Injuries, Traumatic
- Hyperkinesis
- Craniocerebral Trauma
- Trauma, Nervous System
- 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
- Autonomic Agents
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Adrenergic alpha-2 Receptor Agonists
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Sympatholytics
- Propranolol
- Clonidine
Other Study ID Numbers
- 110429
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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