High Altitude Headache
Conditions
Keywords
High Altitude Headache; intra-cranial pressure; hypoxia
Brief summary
The purpose of this study is to determine whether increased pressure in the head is elevated in people who suffer from High Altitude Headache. We hypothesise that head pressure will be elevated in people with High Altitude Headache.
Detailed description
High Altitude Headache is the primary symptom of Acute Mountain Sickness. However, at present the reason why some individuals suffer from High Altitude Headache and others do not remains unknown. It is widely believed that elevated pressure within the brain leads to stretching of pain sensitive fibres and thus headache. However, evidence of raised intracranial pressure during High Altitude Headache is currently unavailable. Therefore, this study aims to examine a proxy measure of intracranial pressure (Optic Nerve Sheath Diameter) in persons visiting High Altitude, half of whom have been given the drug acetazolamide that is known to reduce headache symptoms.
Interventions
DRUGAcetazolamide
During a forty eight hour hypoxic exposure (3777m), subjects will be given either acetazolamide or placebo at hours fifteen, twenty and thirty two.
During a forty eight hour hypoxic exposure (3777m), subjects will be given either acetazolamide or placebo at hours fifteen, twenty and thirty two.
Sponsors
Universita di Verona
North Wales Research Committee, UK
Bangor University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Member of the Italian High Altitude Research Expeditions
Exclusion criteria
* Are under the age of 18years; * sulfonamide allergy * Liver or kidney disfunction * Have any other uncontrolled medical condition * Or are unable to give consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Optic Nerve Sheath Diameter by Ultrasonography | Optic Nerve Sheath Diameter: baseline, 24 hours. | Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Optic nerve sheath diameter obtained by ultrasonography of the eye. Increased optic nerve sheath diameter suggests greater intra cranial pressure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in High Altitude Headache by Visual Analogue Scale | High Altitude Headache: baseline, 24 hours. | Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Outcome measured using visual analogue scale, where 0 mm is no headache and 100 mm is maximum headache. |
| Change in Blood Oxygen Saturation | Blood Oxygen Saturation: baseline, 24 hours. | Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. |
| Change in Fluid Balance | Fluid Balance: baseline, 24 hours. | Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Urine output was recorded by 24 hour urine collection and fluid intake by 24 hour food diaries. Fluid balance was calculated as: (urine output (L) / fluid intake (L) ) \* 100. |
| Change in Optic Nerve Sheath Diameter | Optic Nerve Sheath Diameter: baseline, 3 hours. | Baseline is defined as the average of the 3 hour 12 hour normoxia measurements. 3 hours is defined at the 3 hour hypoxia measurement. |
Countries
United Kingdom
Participant flow
Recruitment details
Participants attending the Antur Ymchwil 2011 Expedition to the European Alps were recruited between 01.07.11 and 01.08.11.
Pre-assignment details
Participants completed two trials, including a 12 hour sea level exposure followed by a 36 hour high altitude exposure (3777m). Participants were assigned to one of two groups based on High-altitude headache susceptibility determined by visual analogue score obtained after 12 hours at high altitude. No participants were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Acetazolamide Arm 1: ACETAZOLAMIDE (250mg) will be given to subjects at fifteen, twenty and thirty two hours post hypoxic exposure (3777m). | 11 |
| Placebo Placebo (LACTOSE MONOHYDRATE) will be given to subjects at fifteen, twenty and thirty two hours post hypoxic exposure (3777m). | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Placebo | Acetazolamide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| Age Continuous | 20 years STANDARD_DEVIATION 1 | 24 years STANDARD_DEVIATION 6 | 21 years STANDARD_DEVIATION 3 |
| Region of Enrollment United Kingdom | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Change in Optic Nerve Sheath Diameter by Ultrasonography
Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Optic nerve sheath diameter obtained by ultrasonography of the eye. Increased optic nerve sheath diameter suggests greater intra cranial pressure.
Time frame: Optic Nerve Sheath Diameter: baseline, 24 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Optic Nerve Sheath Diameter by Ultrasonography | 0.02 mm | Standard Deviation 0.06 |
| Placebo | Change in Optic Nerve Sheath Diameter by Ultrasonography | 0.02 mm | Standard Deviation 0.06 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.98ANOVA
Secondary
Change in Blood Oxygen Saturation
Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement.
Time frame: Blood Oxygen Saturation: baseline, 24 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Blood Oxygen Saturation | 10.8 % oxygen saturation | Standard Deviation 4.3 |
| Placebo | Change in Blood Oxygen Saturation | 11.1 % oxygen saturation | Standard Deviation 4.3 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.2ANOVA
Secondary
Change in Fluid Balance
Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Urine output was recorded by 24 hour urine collection and fluid intake by 24 hour food diaries. Fluid balance was calculated as: (urine output (L) / fluid intake (L) ) \* 100.
Time frame: Fluid Balance: baseline, 24 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Fluid Balance | 342 % of fluid intake | Standard Deviation 109 |
| Placebo | Change in Fluid Balance | 147 % of fluid intake | Standard Deviation 85 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: <0.01ANOVA
Comparison: Post hoc follow up test. T test between acetazolamide and placebo on data at 24 hr time point.p-value: <0.01t-test, 2 sided
Secondary
Change in High Altitude Headache by Visual Analogue Scale
Baseline is defined as the average of the 3 hour and 12 hour normoxia measurement. 24 hours is defined at the 24 hour hypoxia measurement. Outcome measured using visual analogue scale, where 0 mm is no headache and 100 mm is maximum headache.
Time frame: High Altitude Headache: baseline, 24 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in High Altitude Headache by Visual Analogue Scale | 6.4 mm | Standard Deviation 10.5 |
| Placebo | Change in High Altitude Headache by Visual Analogue Scale | 7.2 mm | Standard Deviation 10.5 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.63ANOVA
Secondary
Change in Optic Nerve Sheath Diameter
Baseline is defined as the average of the 3 hour 12 hour normoxia measurements. 12 hours is defined at the 12 hour hypoxia measurement.
Time frame: Optic Nerve Sheath Diameter: baseline, 12 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Optic Nerve Sheath Diameter | 0.01 mm | Standard Deviation 0.04 |
| Placebo | Change in Optic Nerve Sheath Diameter | 0.01 mm | Standard Deviation 0.04 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.98ANOVA
Secondary
Change in Optic Nerve Sheath Diameter
Baseline is defined as the average of the 3 hour and 12 hour normoxia measurements. 36 hours is defined at the 36 hour hypoxia measurement.
Time frame: Optic Nerve Sheath Diameter: baseline, 36 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Optic Nerve Sheath Diameter | 0.01 mm | Standard Deviation 0.04 |
| Placebo | Change in Optic Nerve Sheath Diameter | 0.00 mm | Standard Deviation 0.04 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.98ANOVA
Secondary
Change in Optic Nerve Sheath Diameter
Baseline is defined as the average of the 3 hour 12 hour normoxia measurements. 3 hours is defined at the 3 hour hypoxia measurement.
Time frame: Optic Nerve Sheath Diameter: baseline, 3 hours.
Population: All participants were included. Analysis was intention to treat. There were no missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acetazolamide | Change in Optic Nerve Sheath Diameter | 0.00 mm | Standard Deviation 0.06 |
| Placebo | Change in Optic Nerve Sheath Diameter | -0.01 mm | Standard Deviation 0.06 |
Comparison: Omnibus analysis was performed. 2 (drug: Acetazolamide versus placebo) \* 2 (susceptibility: high altitude headache resistant versus high altitude headache susceptible) \* 6 (time: sea level, 3 \& 12; high altitude, 3, 12, 24 \& 36 hours) analysis of variance with repeated measures on the third factor. Data presented here are for the drug \* time interaction.p-value: 0.98ANOVA