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

NCT01322048 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 110429
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Ventilator-free Days

  Baseline to day 28

Secondary Outcomes (1)

• Plasma Norepinephrine Levels

  Post-treatment (t=Day 8)

Study Arms (2)

Adrenergic Blockade

EXPERIMENTAL

Propranolol and Clonidine

Drug: IV Propranolol and Per Tube Clonidine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

IV Propranolol and Per Tube Clonidine DRUG

1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days

Adrenergic Blockade

Placebo DRUG

Placebo IV q6h and Per Tube q12, both for 7 days

Placebo

Eligibility Criteria

• Age: 16 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead
• Vanderbilt University Medical Center: collaborator
• Eastern Association for the Surgery of Trauma (EAST): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (2)

• Nordness MF, Maiga AW, Wilson LD, Koyama T, Rivera EL, Rakhit S, de Riesthal M, Motuzas CL, Cook MR, Gupta DK, Jackson JC, Williams Roberson S, Meurer WJ, Lewis RJ, Manley GT, Pandharipande PP, Patel MB. Effect of propranolol and clonidine after severe traumatic brain injury: a pilot randomized clinical trial. Crit Care. 2023 Jun 9;27(1):228. doi: 10.1186/s13054-023-04479-6.

  PMID: 37296432 DERIVED

• 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.

  PMID: 23013802 DERIVED

Related Links

• Vanderbilt Multidisciplinary Traumatic Brain Injury Clinic (MTBIC)

MeSH Terms

Conditions

Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries, Traumatic; Psychomotor Agitation; Cognitive Dysfunction

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Dyskinesias; Neurologic Manifestations; Psychomotor Disorders; Neurobehavioral Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mayur B. Patel
• Organization: Vanderbilt University Medical Center

mayur.b.patel@vanderbilt.edu

6153225000

Study Officials

• Mayur B Patel, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery and Neurosurgery

Study Record Dates

• First Submitted: March 2, 2011
• First Posted: March 24, 2011
• Study Start: August 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: December 1, 2016
• Last Updated: August 17, 2017
• Results First Posted: June 8, 2017

Record last verified: 2017-07

Locations

US (1)