Acetazolamide for the Prevention of High Altitude Illness: a Comparison of Dosing

Study Overview
=================
Brief Summary
-----------------
This is a phase 4, randomized, double-blinded interventional trial comparing alternative doses of Acetazolamide for the prevention of High Altitude Illness.

Detailed Description
-----------------
Acetazolamide, or Diamox, is the standard medical prophylaxis agent for high altitude illness. The medication is effective in preventing acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Its mechanism is via inhibition of the carbonic anhydrase enzyme which counteracts the respiratory alkalosis which occurs during ascent to altitude. It facilitates the excretion of bicarbonate in the urine. As a result, acetazolamide hastens acclimatization and helps prevent high altitude disorders. Current recommended dosing is 125 mg, orally twice daily, started 24 hours prior to ascending in elevation. Side effects include tingling of the fingers and toes and perioral numbness which may be erroneously interpreted as stroke symptoms. Since acetazolamide is a mild diuretic, frequent micturition may occur leading to interruption of daytime activities as well as broken sleep. These effects can affect safety at high altitude. Acetazolamide is normally discontinued 2 days after the user has reached their highest elevation or a plateau in elevation. A lower dose may be just as effective in preventing high altitude illnesses while preventing the disconcerting side effects resulting from its use. A smaller dose has not been studied, however. We will compare the common dose of 125 mg twice daily with a lower dose of 62.5 mg twice daily.

Official Title
-----------------
Acetazolamide for the Prevention of High Altitude Illness: a Comparison of Dosing

Conditions
-----------------
Prophylaxis of Acute Mountain Sickness

Intervention / Treatment
-----------------
* Drug: Low Dose Acetazolamide
* Drug: Normal Dose Acetazolamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years or older English or Indian speaking Mountaineers or trekkers who plan to climb Mt. McKinley or trek to Base Camp on Mt. Everest Exclusion Criteria: Low sodium and/potassium blood serum levels Kidney disease or dysfunction Liver disease, dysfunction, or cirrhosis Suprarenal gland failure or dysfunction Hyperchloremic acidosis Angle-closure glaucoma Taking high dose aspirin (over 325 mg/day) Any reaction to sulfa drugs or acetazolamide Pregnant or lactating women

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Acetazolamide normal dose<br>Experimental : Acetazolamide 125 mg twice daily | Drug: Normal Dose Acetazolamide<br>* Administration of normal dose acetazolamide<br>* Other names: Diamox;|
| Experimental: Acetazolamide low dose<br>Experimental: Acetazolamide 62.5 mg twice daily | Drug: Low Dose Acetazolamide<br>* Administration of low dose acetazolamide<br>* Other names: Diamox;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Mountain Sickness as Measured by the Lake Louise Score | Lake Louise Score, A total score of 3 to 5 indicates mild AMS. A score of 6 or more signifies severe AMS. Minimum value - 0, Maximum = 15 | 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Side Effects | The typical side effects of acetazolamide will be measured daily (paresthesias of fingers and toes, change in urination frequency, and change in taste of beverages). The side effect questionnaire included the following questions: In the past 12 h, have you experienced the following symptoms: Tingling of toes? Tingling of fingers? Increase in urination? Taste change of beverages? Symptoms were self-reported and rated on a 0-5 scale (0=none, 5=maximum) | 12 days |