Prophylaxis of Acute Mountain Sickness
Conditions
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.
Interventions
DRUGLow Dose Acetazolamide
Administration of low dose acetazolamide
DRUGNormal Dose Acetazolamide
Administration of normal dose acetazolamide
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Acute Mountain Sickness as Measured by the Lake Louise Score | 12 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Side Effects | 12 days | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acetazolamide Normal Dose Experimental : Acetazolamide 125 mg twice daily
Acetazolamide: Administration of low dose acetazolamide | 43 |
| Acetazolamide Low Dose Experimental: Acetazolamide 62.5 mg twice daily
Acetazolamide: Administration of low dose acetazolamide | 47 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Insufficient altitude reached | 3 | 1 |
| Overall Study | Insufficient data to analyze | 16 | 16 |
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Acetazolamide Normal Dose | Acetazolamide Low Dose | Total |
|---|---|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 12.7 | 41.6 years STANDARD_DEVIATION 13.5 | 43.8 years STANDARD_DEVIATION 13.3 |
| Sex: Female, Male Female | 12 Participants | 14 Participants | 26 Participants |
| Sex: Female, Male Male | 31 Participants | 33 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 47 |
| other Total, other adverse events | 0 / 43 | 0 / 47 |
| serious Total, serious adverse events | 0 / 43 | 0 / 47 |
Outcome results
Primary
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
Time frame: 12 days
Population: Seventy-three participants had sufficient data to be included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide Normal Dose | Number of Participants With Acute Mountain Sickness as Measured by the Lake Louise Score | 21 Participants |
| Acetazolamide Low Dose | Number of Participants With Acute Mountain Sickness as Measured by the Lake Louise Score | 21 Participants |
Secondary
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)
Time frame: 12 days
Population: These participants had sufficient data to be included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetazolamide Normal Dose | Number of Participants With Side Effects | 6 Participants |
| Acetazolamide Low Dose | Number of Participants With Side Effects | 7 Participants |