A Cohort Study Evaluating the Efficacy of PO Magnesium in the Treatment of Acute Traumatic Brain Injury in Adolescents

NCT03475693 | Completed Early Phase 1 FDA Drug

• 1 other identifier: MMMC#1571
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the efficacy of magnesium in symptomatic reduction of mild traumatic brain injury in the adolescent population in the acute setting of injury.

Conditions

Concussion Post Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in symptom severity score

  Using post concussion symptom severity scores, the patient will complete symptom severity scores at specified intervals for comparison in post concussion severity score reduction. Higher scores indicate more severe symptoms, and lower scores indicate less severe symptoms.Post-Concussion Symptom Checklist Rating Mild Mod. Severe Initial 1 Hr. 48 Hr. 120 Hr. Headache 0-6 Nausea 0-6 Vomiting 0-6 Balance Problems 0-6 Dizziness 0-6 Visual Problems 0-6 Fatigue 0-6 Sensitivity to light 0-6 Sensitivity to noise 0-6 Numbness or Tingling 0-6 Pain other than Headache 0-6 Feeling as if "in a fog" 0-6 Feeling Slowed Down 0-6 Difficulty concentrating 0-6 Difficulty remembering 0-6 Drowsiness 0-6 Sleeping less than usual 0-6 Sleeping more than usual 0 1 2 3 4 5 6 Trouble falling asleep 0 1 2 3 4 5 6 More emotional than usual 0-6 Irritability 0-6 Sadness 0-6 Nervousness 0-6 Total Score

  4 scores total, time 0, time 1 hour, time 24 hours, time 120 hours

Secondary Outcomes (1)

• Adverse events in the emergency department

  5 days

Study Arms (2)

Treatment arm

EXPERIMENTAL

Patients will receive PO magnesium 400 mg, Zofran 4 mgODT, and Tylenol 500 mg in the emergency department. They will then continue with 500 mg Tylenol BID and 400 mg MagOx tablets BID for the next 5 days. Symptom severity scores will be obtained and compared throughout this time as mentioned in the study design.

Drug: Magnesium Oxide; Drug: Acetaminophen; Drug: Zofran ODT 4 MG Disintegrating Oral Tablet

Placebo arm

PLACEBO COMPARATOR

Patients will receive PO Zofran 4 mgODT, and Tylenol 500 mg in the emergency department. They will then continue with 500 mg Tylenol BID for the next 5 days. Symptom severity scores will be obtained and compared throughout this time as mentioned in the study design.

Drug: Acetaminophen; Drug: Zofran ODT 4 MG Disintegrating Oral Tablet

Interventions

Magnesium Oxide DRUG

400 mg Magnesium oxide tablet given once in the ED, and prescribed to take BID for 5 days total after discharge

Treatment arm

Acetaminophen DRUG

500 mg tablets given once in the ED, and prescribed to take BID for 5 days total after discharge.

Placebo arm; Treatment arm

Zofran ODT 4 MG Disintegrating Oral Tablet DRUG

Given once in the Emergency department

Placebo arm; Treatment arm

Eligibility Criteria

• Age: 12 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 12 to 18 years
• Presenting chief complaint of headache, head injury, or concussion within the first 48 hours of injury.
• GCS \> 13 on arrival.

You may not qualify if:

• Age \< 12 years or \> 18 years
• Inability to provide informed consent
• Vomiting \> 2 episodes following injury
• Physical or mental disability hindering adequate response to assessment of symptoms
• Hemodynamic instability/medical condition requiring further acute life-saving medical intervention
• Known brain mass, intracranial hemorrhage, skull fracture
• Known contraindications to magnesium use
• Known contraindication to Zofran use

Sponsors & Collaborators

• Corewell Health South: lead
• Michigan State University: collaborator

Study Sites (1)

Lakeland Regional Healthcare

Saint Joseph, Michigan, 49085, United States

Location

Related Publications (16)

• Miller JW, D'Ambrosio R. When basic research doesn't translate to the bedside--lessons from the magnesium brain trauma study. Epilepsy Curr. 2007 Sep-Oct;7(5):133-5. doi: 10.1111/j.1535-7511.2007.00201.x. No abstract available.

  PMID: 17998974 BACKGROUND

• Arango MF, Bainbridge D. Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD005400. doi: 10.1002/14651858.CD005400.pub3.

  PMID: 18843689 BACKGROUND

• Sen AP, Gulati A. Use of magnesium in traumatic brain injury. Neurotherapeutics. 2010 Jan;7(1):91-9. doi: 10.1016/j.nurt.2009.10.014.

  PMID: 20129501 BACKGROUND

• Heath DL, Vink R. Concentration of brain free magnesium following severe brain injury correlates with neurologic motor outcome. J Clin Neurosci. 1999 Nov;6(6):505-9. doi: 10.1016/s0967-5868(99)90011-5.

  PMID: 18639191 BACKGROUND

• Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J, Lucas T, Newell DW, Mansfield PN, Machamer JE, Barber J, Dikmen SS. Magnesium sulfate for neuroprotection after traumatic brain injury: a randomised controlled trial. Lancet Neurol. 2007 Jan;6(1):29-38. doi: 10.1016/S1474-4422(06)70630-5.

  PMID: 17166799 BACKGROUND

• Zhao L, Wang W, Zhong J, Li Y, Cheng Y, Su Z, Zheng W, Guan XD. The effects of magnesium sulfate therapy after severe diffuse axonal injury. Ther Clin Risk Manag. 2016 Sep 27;12:1481-1486. doi: 10.2147/TCRM.S109482. eCollection 2016.

  PMID: 27729796 BACKGROUND

• Heath DL, Vink R. Traumatic brain axonal injury produces sustained decline in intracellular free magnesium concentration. Brain Res. 1996 Oct 28;738(1):150-3. doi: 10.1016/0006-8993(96)00957-2.

  PMID: 8949939 BACKGROUND

• Giza CC, Hovda DA. The new neurometabolic cascade of concussion. Neurosurgery. 2014 Oct;75 Suppl 4(0 4):S24-33. doi: 10.1227/NEU.0000000000000505.

  PMID: 25232881 BACKGROUND

• McIntosh TK, Faden AI, Yamakami I, Vink R. Magnesium deficiency exacerbates and pretreatment improves outcome following traumatic brain injury in rats: 31P magnetic resonance spectroscopy and behavioral studies. J Neurotrauma. 1988;5(1):17-31. doi: 10.1089/neu.1988.5.17.

  PMID: 3193462 BACKGROUND

• Hoane MR. Assessment of cognitive function following magnesium therapy in the traumatically injured brain. Magnes Res. 2007 Dec;20(4):229-36.

  PMID: 18271492 BACKGROUND

• Busingye DS, Turner RJ, Vink R. Combined Magnesium/Polyethylene Glycol Facilitates the Neuroprotective Effects of Magnesium in Traumatic Brain Injury at a Reduced Magnesium Dose. CNS Neurosci Ther. 2016 Oct;22(10):854-9. doi: 10.1111/cns.12591. Epub 2016 Jul 15.

  PMID: 27421816 BACKGROUND

• Cernak I, Vink R, Zapple DN, Cruz MI, Ahmed F, Chang T, Fricke ST, Faden AI. The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats. Neurobiol Dis. 2004 Oct;17(1):29-43. doi: 10.1016/j.nbd.2004.05.011.

  PMID: 15350963 BACKGROUND

• McKee JA, Brewer RP, Macy GE, Borel CO, Reynolds JD, Warner DS. Magnesium neuroprotection is limited in humans with acute brain injury. Neurocrit Care. 2005;2(3):342-51. doi: 10.1385/NCC:2:3:342.

  PMID: 16159086 BACKGROUND

• Vollmer BL, Kirkwood MW, Comstock RD, Currie D, Grubenhoff JA. Assessing the Clinical Utility of the Question, "Is Your Child/Are You Back to Normal?" in Pediatric Concussion Symptom Resolution. Clin Pediatr (Phila). 2018 Feb;57(2):146-151. doi: 10.1177/0009922817693300. Epub 2017 Feb 15.

  PMID: 28198194 BACKGROUND

• Randolph C, Millis S, Barr WB, McCrea M, Guskiewicz KM, Hammeke TA, Kelly JP. Concussion symptom inventory: an empirically derived scale for monitoring resolution of symptoms following sport-related concussion. Arch Clin Neuropsychol. 2009 May;24(3):219-29. doi: 10.1093/arclin/acp025. Epub 2009 Jun 23.

  PMID: 19549721 BACKGROUND

• Li W, Bai YA, Li YJ, Liu KG, Wang MD, Xu GZ, Shang HL, Li YF. Magnesium sulfate for acute traumatic brain injury. J Craniofac Surg. 2015 Mar;26(2):393-8. doi: 10.1097/SCS.0000000000001339.

  PMID: 25723660 RESULT

Related Links

• Zofran FDA label

MeSH Terms

Conditions

Post-Concussion Syndrome

Interventions

Magnesium Oxide; Acetaminophen; Ondansetron

Condition Hierarchy (Ancestors)

Brain Concussion; Head Injuries, Closed; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Wounds and Injuries; Wounds, Nonpenetrating

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Oxides; Oxygen Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Christopher Trigger, MD, CAQSM

  Lakeland Regional Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients will be assigned a 3 digit number given at random and treatment arm will be randomized to day of presentation with treatment determined by even or odd day of the month
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, prospective, cohort study comparing two non-invasive treatments for Mild traumatic brain injury in patients ages 12-18 that present to the Lakeland Health Emergency departments in either St. Joseph, MI or Niles, MI.

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: March 23, 2018
• Study Start: September 1, 2017
• Primary Completion: November 30, 2019
• Study Completion: December 30, 2019
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)