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

November 20, 2020 updated by: Spectrum Health - Lakeland
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction Mild traumatic brain injuries are a growing problem in sports, and are now becoming publicly relevant. Mild traumatic brain injuries account for 700,000 ED visits, hospitalizations, and deaths annually. Today, 1 out of 5 adolescents will be affected by mild traumatic brain injuries. Magnesium is a critical neuromodulator that plays an important role in controlling neural signaling in the brain, and studies have shown a transiently low level of magnesium in CNS neurons following traumatic brain injury. If these electrolyte imbalances could be corrected with magnesium supplementation during the acute injury, this could potentially decrease the symptomatic period in those with mild TBI. The investigators aim to show a correlation between administration of PO magnesium and increased resolution of symptoms thereby improving the subjective recovery course of adolescents with concussion.

Study objective This randomized, cohort study will compare the clinical efficacy of PO magnesium and Zofran, to that of PO Tylenol and Zofran in the treatment of adolescents presenting within 48 hours of a mild traumatic brain injury.

Purpose With current studies and the sports media revolving around the long-term effects of repetitive mild TBI, it is important to continue to improve treatment of these injuries. Current therapy revolves around symptomatic care, rest, and return to school/sport after symptoms have resolved and the patient has been cleared by a physician. After a concussion, there is a period of 7-10 days where the patient has a transient decrease in the participants mental functioning. The investigators hope to decrease the length of the acute symptomatic period by supplementing oral magnesium along with the current symptomatic care. Studies have shown that IV magnesium in high doses can improve the function of patients with severe TBI. There have not been many studies looking at the efficacy of PO magnesium in this setting. While there is no evidence that concussions have long term effects on neurocognitive function, this study could add to the existing algorithm for concussion management.

Hypothesis The investigators believe that administration of magnesium in patients who present with mild traumatic brain injuries will decrease post concussive symptoms, thereby speeding recovery.

Methods Study design and setting Randomized, prospective, parallel 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. The data collection period will take approximately 2 years with a minimum goal of 76 patients enrolled in the study.

Patient selection Patients ages 12-18 presenting to the emergency department with a mild traumatic brain injury and GCS >13 meeting inclusion criterial will be provided a study participation form to receive informed consent. ED staff will assess the patient's symptom severity with the Concussion Symptom Severity Score listed below. After this ED staff will assess the patient for inclusion criteria, followed by a healthcare provider Exclusion criteria will be evaluated by the healthcare provider at this time, and medical therapy can be initiated.

Inclusion criteria

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

Exclusion criteria

  • 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

Interventions Informed consent will be obtained after initial assessment of the patient by the healthcare provider, and inclusion/exclusion criteria are met.

After informed consent is obtained, and the patient meets the criteria for further acceptance into the study, then the patient's current symptoms will be screened by the healthcare providers. This will be the symptom score at time "0". After this the participants will receive 1 of 2 therapies that will be randomized by date of service whether it is an odd or even date. The treatment arm of the study (Even Days) will include 800mg of oral magnesium oxide along with a 4mg Zofran ODT as an initial dose in the emergency department. These participants will then continue to take 2 tablets of prescribed Magnesium oxide 400mg daily until their follow up with a physician at a local sports medicine clinic. The placebo arm (Odd days) of the study will receive 650 mg Acetaminophen, and a 4mg Zofran ODT in the emergency department. These participants continue to take scheduled acetaminophen 500 mg q8hr until follow up with a physician in the sports medicine clinic. The participants will have their symptom score re-evaluated after 1 hour of observation. If stable they will be discharged. A 24 hour follow up phone conversation will be placed by the primary investigators for a repeat of their symptom severity score. Finally, the participant will follow up in the outpatient sports medicine concussion clinic at 120 hours where a 4th symptom severity score will be obtained. These data will be collected and analyzed to compare the overall change in symptom severity score between the two treatment arms. The Aim of this study is to have a total n > 76. This will likely require 2 years of data collection. Our primary endpoint will be to evaluate if magnesium has an impact on participant's post-concussion severity index and a change in symptom severity score over time.

Symptom assessment Symptom assessment primarily described above, the investigators will use the standardized Post Concussion Severity. If the participant continues to have pain and a further intervention is required outside of the treatment and placebo arm the investigators will provide Ibuprofen weight adjusted for the participant's weight.

ED staff will re-assess the participant and record level of pain at time of study drug administration and at 60 minutes after study drug administration.

Data collection Primary data collection through the Concussion symptom severity index. Outcome measures Primary outcome is a comparison between the treatment and placebo groups in their changes in symptom severity scores over a 5-day period. Secondary endpoints include development of adverse effects related to medication administration, need for further intervention in the emergency department, and whether the participant's have returned to their baseline function by 120 hours.

Data analysis To be coordinated with Dr. William Corser, and an associated statistician team through Michigan State University. The study design will be a randomized cohort, repeat-measures efficacy study. The analysis of study results will look at data categorically, involving case or control group, and will also evaluate symptom scores at set intervals. An independent sample t test comparing the mean symptom severity scores among the cases and control groups at initial time of entry into the study, followed by repeat measurements after 1 hour, 24 hours and 120 hours will then be conducted. Point biserial correlation testing will also be employed to measure the strength of the relationship between being a member of either the case or control group with symptom severity scores. The primary outcome of this study will be the comparison of symptom severity scores between the treatment and placebo groups over a 5-day period. Anticipated secondary outcomes include but are not limited to adverse effects relating to medications administered, need for further intervention in the emergency department and return to baseline function within 120 hours.

Ethical Considerations Risks The risks of this study are minimal and related to the administration of medications. Acetaminophen, Zofran, and magnesium have low risk for development of adverse effects.

If an adverse reaction to these medications is to occur, while unlikely, the participant will be treated for these reactions symptomatically. Further medication administration will be based on the ED provider's discretion at the current standard of care and the participant's reactions will be documented/included in the secondary outcomes of the study.

Benefits Participant benefits include potential decreased duration of symptoms in the acute phase of injury following concussion. Magnesium is a relatively benign medication that is used frequently, and if this can contribute positively to acute concussion management, the investigators hope to change how mild traumatic brain injuries are managed.

Risk/benefit ratio Benefits of subject participation outweighs risk. Current standard of care is symptomatic care with rest, and follow up if symptoms persist 5-7 days following initial intervention. Adding magnesium, which has a low adverse effect profile and is an inexpensive option that could have a large impact on concussion management.

Participation Duration Participation in the proposed study will last the duration of their emergency department visit. Participation will involve a minimum of 30-60 minutes. The continued participation through the next 5 days is critical to the study to allow proper follow up, along with medication dosing.

Rationale for the use of selected subject population Concussions are a growing problem with socialization and media attention nationally. While there are no long term effects of concussions, there is an acute phase of injury that if decreased would benefit those with mild traumatic brain injury. With adolescents, there is a drive to return to normal health, and often an immediacy for treatment allowing appropriate initial intervention and follow up in the outpatient office prior to returning to daily activities. The interventions proposed in this study contain the current standard of care, thereby the addition of magnesium supplementation is medically benign but could have physiologic potential.

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Saint Joseph, Michigan, United States, 49085
        • Lakeland Regional Healthcare

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • • 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.

Exclusion Criteria:

  • • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm
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
400 mg Magnesium oxide tablet given once in the ED, and prescribed to take BID for 5 days total after discharge
Drug: Acetaminophen
500 mg tablets given once in the ED, and prescribed to take BID for 5 days total after discharge.
Drug: Zofran ODT 4 MG Disintegrating Oral Tablet
Given once in the Emergency department
Placebo Comparator: Placebo arm
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
500 mg tablets given once in the ED, and prescribed to take BID for 5 days total after discharge.
Drug: Zofran ODT 4 MG Disintegrating Oral Tablet
Given once in the Emergency department

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in symptom severity score
Time Frame: 4 scores total, time 0, time 1 hour, time 24 hours, time 120 hours
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events in the emergency department
Time Frame: 5 days
Patients who require further treatment in the ED, require further medications, or develop adverse effects to the medications prescribed.
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spectrum Health - Lakeland

Collaborators

Michigan State University

Investigators

  • Principal Investigator: Christopher Trigger, MD, CAQSM, Lakeland Regional Health System

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2017

Primary Completion (Actual)

November 30, 2019

Study Completion (Actual)

December 30, 2019

Study Registration Dates

First Submitted

August 8, 2017

First Submitted That Met QC Criteria

March 22, 2018

First Posted (Actual)

March 23, 2018

Study Record Updates

Last Update Posted (Actual)

November 24, 2020

Last Update Submitted That Met QC Criteria

November 20, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MMMC#1571

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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