Comparison of Metoclopramide and Ibuprofen for the Treatment of Acute Mountain Sickness

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to determine the efficacy of metoclopramide in relieving the symptoms of Acute Mountain Sickness (AMS). It is our hypothesis that the combined antiemetic and analgesic effects of metoclopramide (which has been study-proven to be effective in relieving symptoms of migraine headache) will prove to be more efficacious in relieving symptoms of acute mountain sickness than the standard, previously-studied analgesic medication, ibuprofen.

Detailed Description
-----------------
Acute Mountain Sickness (AMS) is a well described disease process that occurs as a result of rapid exposure to high altitude. High altitude headache (HAH) is defined as the presence of headache in the setting of a recent increase in altitude. When HAH is associated with nausea, vomiting, fatigue, weakness, dizziness, lightheadedness or poor sleeping, AMS is diagnosed. While benign, AMS is very common, afflicting up to 80 % of travelers who ascend rapidly to 14,000 ft, and can be debilitating. AMS is thought to occur secondary to hypoxia-induced cerebral vasodilation. The antiemetic metoclopramide has been well studied and is commonly administered for treatment of migraine headaches in emergency departments across the U.S. The symptoms of migraine headaches are often similar to those of AMS. The mechanism of metoclopramides beneficial effect in this indication appear to be a result of its antagonism of central and peripheral dopamine receptors,most notably by blocking stimulation of the medullary chemoreceptor trigger zone. No studies have yet evaluated the potential benefits of metoclopramide for the relief of AMS. In contrast, ibuprofen has been well studied and found to be an effective treatment for the relief of symptoms of high altitude headache and AMS. The study will be a convenience sample of trekkers traveling through the Annapurna Circuit in Nepal during the 3 month time period of March-May, 2012. Subjects will be recruited from visitors to Manang, Nepal staying in local hostels, those visiting the Himalayan Rescue Association clinic in Manang, and those responding to locally posted signage regarding study enrollment. Eligible patients will be consented and enrolled in the study. Patients will be randomized to receive either Ibuprofen 400mg or Metoclopramide 10mg by mouth. Investigators will be blinded as to which arm of the study the patient is enrolled. Participants will be assessed by Lake Louise Score and Visual Analog Scale for headache and nausea severity immediately prior to ingestion of study medication, and then serially at 30, 60, and 120 minutes following medication ingestion. Standard statistical analysis of the Lake Louise AMS scores and visual analog scales will be used to determine which medication is more effective in treating acute mountain sickness.

Official Title
-----------------
Acute Mountain Sickness Treatment: A Double-blind Comparison of Metoclopramide vs. Ibuprofen

Conditions
-----------------
Acute Mountain Sickness, High Altitude Headache

Intervention / Treatment
-----------------
* Drug: Ibuprofen
* Drug: Metoclopramide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Presence at Manang recruitment center (at approximately 11,500 ft) during the dates March through May, 2012. Recent increase in altitude of > 1000 ft vertical in last 24 hours Presence of headache and at least one other symptom required for diagnosis of acute mountain sickness (including nausea, vomiting, fatigue, weakness, dizziness, lightheadedness or poor sleeping.) Exclusion Criteria: Age less than 19 years old Known allergy or contraindication to either ibuprofen or metoclopramide Evidence of severe high altitude illness (e.g. High altitude pulmonary edema (HAPE) as evidenced by dyspnea at rest -- or of High Altitude Cerebral Edema (HACE) as evidenced by altered mental status or ataxia) Known or suspected pregnancy Use of other analgesic or antiemetic within 8 hours of study enrollment History of migraines or other chronic headache disorders Inability to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metoclopramide<br>150 subjects with acute mountain sickness will be randomly assigned to take metoclopramide. | Drug: Metoclopramide<br>* Metoclopramide 10mg tablet. Take one tablet by mouth.<br>* Other names: Reglan;|
| Active Comparator: Ibuprofen<br>150 subjects with acute mountain sickness will be randomly assigned to take ibuprofen. | Drug: Ibuprofen<br>* Ibuprofen 400mg tablet. Take one dose by mouth.<br>* Other names: Motrin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache and Nausea Visual Analog Scales | Subjects will complete 100mm visual analog scales of both headache and nausea at time zero, 30, 60, and 120 minutes after taking the study medication. Visual analog scales are a valid assessment of symptom severity for acute mountain sickness. | 120 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lake Louise Acute Mountain Sickness Score | Subjects will take the Lake Louise Acute Mountains Sickness score before taking the medication and 120 minutes after taking the medication. The Lake Louise Acute Mountain Sickness Score is a standard measure of the severity of acute mountain sickness and is commonly used in studies involving acute mountain sickness. | 120 minutes | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nepal, Acute Mountain Sickness, High Altitude Headache, Lake Louise AMS Score, Visual Analog Scale, Ibuprofen, Metoclopramide