Intracranial Pressure in Experimental Models of Headache

Study Overview
=================
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.

Official Title
-----------------
Intracranial Pressure in Experimental Models of Headache

Conditions
-----------------
High Altitude Headache

Intervention / Treatment
-----------------
* Drug: Acetazolamide
* Drug: Lactose monohydrate


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>Arm 1: ACETAZOLAMIDE (250mg) will be given to subjects at fifteen, twenty and thirty two hours post hypoxic exposure (3777m). | Drug: Acetazolamide<br>* During a forty eight hour hypoxic exposure (3777m), subjects will be given either acetazolamide or placebo at hours fifteen, twenty and thirty two.<br>* Other names: Diamox;|
| Placebo Comparator: Placebo<br>Placebo (LACTOSE MONOHYDRATE) will be given to subjects at fifteen, twenty and thirty two hours post hypoxic exposure (3777m). | Drug: Lactose monohydrate<br>* During a forty eight hour hypoxic exposure (3777m), subjects will be given either acetazolamide or placebo at hours fifteen, twenty and thirty two.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Optic Nerve Sheath Diameter: baseline, 24 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | High Altitude Headache: baseline, 24 hours. | 
| 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. | Blood Oxygen Saturation: baseline, 24 hours. | 
| 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. | Fluid Balance: baseline, 24 hours. | 
| 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. | Optic Nerve Sheath Diameter: baseline, 3 hours. | 
| 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. | Optic Nerve Sheath Diameter: baseline, 12 hours. | 
| 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. | Optic Nerve Sheath Diameter: baseline, 36 hours. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
High Altitude Headache; intra-cranial pressure; hypoxia