Study Description

Migraine or severe headache affected one-fifth of women and one-tenth of men in 2015 and is one of the leading causes of disability in the world. Over one million visits to emergency departments (ED) in the US are due to migraines. Migraine, previously believed to be a vascular disorder, is caused by inflammation due to vasodilation in the meninges secondary to the release of vasoactive neuropeptides by stimulation of the trigeminal nerve. This inflammation can result in symptoms such as headache, nausea, vomiting, dizziness, photophobia and phonophobia.

Despite migraine being a common disorder, there has yet to be a cure. Several classes of medications have been studied for the treatment of migraine. Recently, conventional therapy has shifted to the use of antidopaminergics including prochlorperazine, metoclopramide and haloperidol, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and triptans, sumatriptan being the most commonly utilized. 5Although intravenous opioids have historically been the most common treatment for migraines, their use has fallen out of favor due to their association with increased recurrence of headaches and ED visits, abuse potential, and most recently severe intravenous opiate shortage. Alternative treatments include ketamine, propofol, dihydroergotamine and magnesium.

Magnesium is an intracellular cation that has been associated with both the function of serotonin and regulation of vascular tone, which are both mechanisms that implicate its role in the treatment of migraine. Intravenous magnesium sulfate has been studied as a treatment for migraine compared to placebo, metoclopramide and prochlorperazine. These studies have shown that magnesium is well-tolerated with a good safety profile and may be efficacious in the treatment of migraine. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. However, no trial has evaluated these modalities simultaneously in the same population. The purpose of our study is to compare the relative efficacy for magnesium, metoclopramide, and prochlorperazine in the treatment of headache and migraine.

Via monthly block randomization, patients will be given one of three guideline recommended study drugs. Allocation will be concealed by a pharmacist (not participating in the rest of the study) solely designated to choose which drug will be the assigned study drug for each month. The pharmacists, physicians, and nurses participating in administration of the medications will be blinded to which drug is being administered during each month. Metoclopramide, prochlorperazine and magnesium have been recommended in clinical practice guidelines and have become routine standard of care for treatment of migraine in this emergency department. All three study drugs will be stored in the investigational medication refrigerator located in the main pharmacy. A pharmacist on duty in the emergency department will obtain the medication from the refrigerator and deliver it to the bedside nurse who is actively caring for the patient after an order from the physician.

The primary outcome of this study will be mean change in pain from baseline to 30 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale. Secondary endpoints include mean change in pain from baseline to 60 minutes and 120 minutes after initiation of infusion (as defined on a 11-point Numeric Rating Scale), time to emergency department discharge, and adverse effects due to administration of study drug (hypotension, flushing, akathisia, dystonia, nausea, vomiting, dizziness, drowsiness, other self-reported adverse effects).

Condition or Disease	Intervention/Treatment
Migraine Headache	Drug: Magnesium Sulfate Drug: Metoclopramide 10mg Drug: Prochlorperazine (Compazine) Injection

Study Design

Study Type	Interventional
Actual Enrollment	157 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Quadruple
Primary Purpose	Treatment
Official Title	A Randomized, Placebo-Controlled, Double-Blind Study of the Effects of Magnesium Compared to Conventional Therapy on Acute Migraine
Study Start Date	August 23, 2019
Actual Primary Completion Date	March 31, 2020
Actual Study Completion Date	April 6, 2023

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Magnesium Magnesium Sulfate 2gm in 50ml D5W over 20 minutes	Drug: Magnesium Sulfate Magnesium Sulfate 2gm in 50ml D5W over 20 minutes
Metoclopramide Metoclopramide 10mg in 50ml D5W over 20 minutes	Drug: Metoclopramide 10mg
Prochlorperazine Prochlorperazine in 50ml D5W over 20 minutes	Drug: Prochlorperazine (Compazine) Injection

Outcome Measures

Primary Outcome Measures

1. 30 Minute Pain Score [30 minutes after initiation]
   Scores range from 0-10. A higher score, denotes more pain

Secondary Outcome Measures

1. Length of Stay [From time of arrival to time of discharge.]
   Emergency Department Length of stay. Measured from time of arrival to time of discharged documented in the electronic medical record.
2. Need for Rescue Analgesia [From time of arrival to time of discharge.]
   Percentage of participants who had necessity for rescue analgesics after study drug administration

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	Yes
Inclusion Criteria	Age > 18 years or older Able to provide informed consent Primary diagnosis of headache or migraine Between October 1, 2018 to April 1, 2020 Presenting to Advocate Christ Medical Center emergency department and meet clinical assessment per physician
Exclusion Criteria	Pregnancy defined as a positive urine HCG Stated history of renal impairment Allergy or sensitivity to any study drugs Concomitant treatment at the time of study drug administered in the emergency department Patients with a history of this study participation

Contacts and Locations

Sponsors and Collaborators	Wake Forest University Health Sciences
Locations	Advocate Christ Medical Center | Oak Lawn, Illinois, United States, 60453
Investigators	Principal Investigator: Michael Cirone, MD, advocate christ medical center

Study Documents (Full Text)

• Documents Provided by Wake Forest University Health Sciences: Study Protocol and Statistical Analysis Plan September 10, 2020

More Information

Additional Relevant MeSH Terms

• Migraine Disorders
• Headache
• Headache Disorders, Primary
• Headache Disorders
• Brain Diseases
• Central Nervous System Diseases
• Nervous System Diseases
• Pain
• Neurologic Manifestations