Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE) (D4H)
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|ClinicalTrials.gov Identifier: NCT03341676|
Recruitment Status : Suspended (COVID)
First Posted : November 14, 2017
Last Update Posted : November 24, 2020
|Condition or disease||Intervention/treatment||Phase|
|High Altitude Cerebral Edema||Drug: Dexamethasone Drug: Placebo||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Double-blind, randomised controlled trial|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Masking Description:||The participant, Investigator supervising the visit and the Outcome Assessor will be blinded to the treatment allocation|
|Official Title:||Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)|
|Actual Study Start Date :||January 14, 2019|
|Estimated Primary Completion Date :||September 4, 2021|
|Estimated Study Completion Date :||September 4, 2021|
8ml IV 3.3mg/mL dexamethasone
Dexamethasone 3.3 mg/mL solution for injection
Placebo Comparator: Placebo
8ml IV 0.9% w/v saline
Sodium Chloride 0.9% w/v solution for injection
- Differences in oedematous changes in the brain and spinal cord [ Time Frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult ]Differences in oedematous changes in the brain and spinal cord as measured by changes in brain and spinal cord MRI imaging
- Primary blood brain barrier breakdown in hypoxic cytotoxic oedema [ Time Frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult ]To assess the role of primary blood brain barrier breakdown in hypoxic cytotoxic oedema as measured by variation in serum markers
- Assessing the usefulness of biomarkers of hypoxic cerebral changes. [ Time Frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult ]Change in glial specific (GFAP) and non-glial specific (purines) serum biomarkers from baseline and at 8, 11, 22 and 26 hours post hypoxic insult
- Spinal cord model [ Time Frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult ]To develop a hypoxic spinal cord model for use in future research looking into complex vascular surgery.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03341676
|University Hospitals Coventry and Warwickshire NHS Trust|
|Coventry, West Midlands, United Kingdom, CV2 2DX|
|Principal Investigator:||Christopher Imray, PhD MBBS||University Hospital Coventry and Warwickshire NHS Trust|