Brief Title
Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)
Official Title
Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)
Brief Summary
When the brain detects a drop in oxygen levels in the blood (hypoxia) there is a compensatory
increase in blood flow. Acute mountain sickness (AMS) is a cluster of symptoms which commonly
occur in those ascending to high altitude and experiencing hypoxia due to increased blood
flow and then swelling in the brain. Symptoms include headache, nausea, insomnia and fatigue.
The exact mechanisms by which AMS develops remains poorly understood. Dexamethasone has been
shown to reduce the risk of developing significant brain swelling in other settings.
Therefore we hypothesise that administering low dose Dexamethasone could protect against
hypoxia induced cerebral and spinal oedema.
Detailed Description
The exact mechanisms by which AMS develops remains poorly understood. Interestingly, brain
and spinal cord swelling due to low oxygen levels can also occur in the period following
surgery to treat thoracic and abdominal aortic aneurysms, dangerous swellings of the major
blood vessel in the body. Therefore, if we find a therapeutic benefit of receiving a dose of
Dexamethasone in a controlled, reversible setting of hypoxia, it is possible that this could
be useful in the treatment of post-operative hypoxia as well.
Work with MRI imaging has demonstrated reduced measures of water movement in patients
suffering from cerebral or spinal ischaemia, due to swelling. Specific water channels in
brain cells (astrocytes) are involved in the movement of water, and Dexamethasone has been
shown to reduce expression of these channels in animal models. Dexamethasone already plays a
role in lowering pressure in the brain in the setting of brain tumours. Although high doses
are typically used in this setting, there is evidence that lower doses may be equally
effective, especially in patients with less severe swelling.
Subjects will be consented and randomised in the weeks before the actual study.
Before entering the tent, the following data will be collected:
- Lake Louise Acute Mountain Sickness self-assessment questionnaire
- Pulse oximetry
- Non-invasive cardiac monitoring (ECG)
- End tidal CO2
- Venous blood collection (Full blood count, renal function, S100 and GFAP)
- Finger-prick blood collection (Purines)
- Magnetic Resonance Angiography
Non-invasive monitoring will continue every 2 hours at the start of the study and around the
time of administration of the study drug. They will continue at less frequent intervals
throughout the study period. This includes ECG trace and an AMS self-assessment
questionnaire.
Venous sampling will be performed on 5 occasions throughout the study. Finger prick sampling
will be done at the same time points
Each subject will have 5 MRI scans during the course of the study.
Subjects will be begin hypoxication 1 hour after entering the tent. They will be returned to
normal oxygen levels after 24 hours.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Differences in oedematous changes in the brain and spinal cord
Secondary Outcome
Primary blood brain barrier breakdown in hypoxic cytotoxic oedema
Condition
High Altitude Cerebral Edema
Intervention
Dexamethasone
Study Arms / Comparison Groups
Dexamethasone
Description: 8ml IV 3.3mg/mL dexamethasone
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
January 14, 2019
Completion Date
March 31, 2023
Primary Completion Date
March 31, 2023
Eligibility Criteria
Inclusion Criteria:
- Provision of informed consent
- Healthy men and women aged 20-50 years
- Ability to fully understand the requirements of the protocol
- Negative pregnancy
- BMI <30 kg/m2
Exclusion Criteria:
- Recent experience of high altitude: Any subject who has visited high altitudes
(defined as 8,000 - 12,000 feet above sea level) within 4 weeks of starting the study.
- Abnormal blood pressure: AHA guidelines state blood pressures ≥140/90 mmHg require
medical management. Patients with a blood pressure above these parameters will be
excluded.
- Any evidence of systemic infection e.g. respiratory tract infection.
- Any evidence of renal disease (i.e. eGFR <60, as this precludes intravenous contrast
required for MRI scan)
- History of Tuberculosis
- History of heart disease
- Conditions including but not limited to: Glaucoma (including family history), ocular
herpes simplex (risk of corneal perforation), severe affective disorders (particularly
if history of steroid-induced psychosis), epilepsy, peptic ulcer, hypothyroidism,
history of steroid myopathy, ulcerative colitis, diverticulitis, recent intestinal
anastomoses, thromboembolic disorders or myasthenia gravis.
- Breastfeeding
- Current smoker
- Contraindications for MRI
- Known sensitivity to the study drug and / or it's excipients: History of
hypersensitivity to steroids (any preparation).
- Taking pharmaceutical preparations or over the counter medications known to interact
with intravenous Dexamethasone.
- Current participation in other interventional research
Gender
All
Ages
20 Years - 50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Christopher Imray, PhD MBBS, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT03341676
Organization ID
CI175716
Responsible Party
Sponsor
Study Sponsor
University Hospitals Coventry and Warwickshire NHS Trust
Study Sponsor
Christopher Imray, PhD MBBS, Principal Investigator, University Hospital Coventry and Warwickshire NHS Trust
Verification Date
June 2022