Brain InjuriesPhase 2NCT01322048
DASH After TBI Study: Decreasing Adrenergic or Sympathetic Hyperactivity After Traumatic Brain Injury
A Phase 2 study testing IV Propranolol and Per Tube Clonidine in people with Brain Injuries and Craniocerebral Trauma, run by Vanderbilt University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 64 years
- Conditions the study is for
- Brain Injuries, Craniocerebral Trauma, Trauma, Nervous System
- What is being tested?
- IV Propranolol and Per Tube Clonidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 64 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
About this study
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
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.
Read the 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.
- Being tested
- IV Propranolol and Per Tube Clonidine, Placebo
- Keywords
- Sympathetic Hyperactivity, Traumatic Brain Injury, Agitation, Severe TBI, TBI, Catecholamines, Heart rate variability, Adrenergic alpha-Agonists, Adrenergic beta-Antagonists, Cognitive Impairment
- Medical subject headings
- Brain Injuries, Craniocerebral Trauma, Trauma, Nervous System, Brain Injuries, Traumatic, Psychomotor Agitation, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV Propranolol and Per Tube ClonidineDrug
1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days
PlaceboDrug
Placebo IV q6h and Per Tube q12, both for 7 days
| Study group | Role | What they receive |
|---|---|---|
| Adrenergic Blockade | Experimental | Propranolol and Clonidine Receives: Drug: IV Propranolol and Per Tube Clonidine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventilator-free Days
Measured: Baseline to day 28
Secondary outcomes (1)
Plasma Norepinephrine Levels
Measured: Post-treatment (t=Day 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2011 (estimated)
- Study startAug 2011
- Primary completionJan 2015
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain InjuriesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt University Medical Center, Eastern Association for the Surgery of Trauma (EAST)
- Responsible party
- Principal investigator, Mayur Patel, Vanderbilt University
- Investigators
- Mayur B Patel, MD, MPH, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01322048
- Sponsor's protocol ID
- 110429
- Status last verified
- Jul 2017
- First submitted
- 2 Mar 2011
- Last updated
- 17 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37296432Patel 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.
PubMed 23013802
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01322048
- Acronym / sponsor ID
- 110429
- Keywords
- Sympathetic Hyperactivity, Traumatic Brain Injury, Agitation, Severe TBI, TBI, Catecholamines, Heart rate variability, Adrenergic alpha-Agonists
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- Vanderbilt University Medical Center, Eastern Association for the Surgery of Trauma (EAST)
- Study start
- Aug 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 24 Mar 2011 (estimated)
- Results
- Posted 8 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adrenergic Blockade | Experimental | Drug: IV Propranolol and Per Tube ClonidinePropranolol and Clonidine |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 16 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV Propranolol and Per Tube Clonidine1 mg IV q6h Propranolol and 0.1 mg Per Tube Clonidine, both for 7 days | Drug | Adrenergic Blockade |
| PlaceboPlacebo IV q6h and Per Tube q12, both for 7 days | Drug | Placebo |
Primary outcome
Ventilator-free Days
Time frame: Baseline to day 28
1 secondary outcome
Plasma Norepinephrine Levels
Time frame: Post-treatment (t=Day 8)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37296432Nordness 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.
- Derived from this study: PubMed 23013802Patel 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.
- Vanderbilt Multidisciplinary Traumatic Brain Injury Clinic (MTBIC)Link provided by the sponsor.
Related trials for Brain Injuries
Recruiting
Amnioinfusion's Protective Effects on Respiratory and Longitudinal Pediatric Outcomes After Intrapartum Meconium Exposure
Neonatal Respiratory Distress Related Conditions, Meconium
Recruiting
Evaluating Long-term Use of a Pediatric Robotic Exoskeleton (P.REX/Agilik) to Improve Gait in Children With Movement Disorders
Cerebral Palsy, Muscular Dystrophy
RecruitingPhase 1
Rehabilitation Through Virtual Immersion & Integrated Exposure for Mild Traumatic Brain Injury (ReVIVE for mTBI)
Traumatic Brain Injuries, TBI (Traumatic Brain Injury)
RecruitingObservational study
Study of Sagittal Pelvic Statics in the Sitting Position in Children With Cerebral Palsy
Cerebral Palsy Infantile
Not yet recruitingObservational study
Turkish Translation, Cross-Cultural Adaptation, Validity, and Reliability of the ABILHAND-Kids Young CP Scale
Cerebral Palsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mayur B Patel, MD, MPH principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV Propranolol and Per Tube Clonidine in people with Brain Injuries and Craniocerebral Trauma, run by Vanderbilt University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator-free Days (time frame: Baseline to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01322048, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2017.