Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)

High Altitude Cerebral Edema Clinical Trial

— D4H  

Official title:

Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03341676
• Other study ID #: CI175716
• Status: Completed
• Phase: Phase 1
• Start date: January 14, 2019
• Est. completion date: August 31, 2023

Study information

• Verified date: June 2024
• Source: University Hospitals Coventry and Warwickshire NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Altitude Sickness
• Brain Edema
• Edema
• High Altitude Cerebral Edema

Intervention

Drug:
• Dexamethasone
Dexamethasone 3.3 mg/mL solution for injection
• Placebo
Sodium Chloride 0.9% w/v solution for injection

Locations

Country	Name	City	State
United Kingdom	University Hospitals Coventry and Warwickshire NHS Trust	Coventry	West Midlands

Sponsors (1)

Lead Sponsor	Collaborator
University Hospitals Coventry and Warwickshire NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in oedematous changes in the brain and spinal cord	Differences in oedematous changes in the brain and spinal cord as measured by changes in brain and spinal cord MRI imaging	0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Secondary	Primary blood brain barrier breakdown in hypoxic cytotoxic oedema	To assess the role of primary blood brain barrier breakdown in hypoxic cytotoxic oedema as measured by variation in serum markers	0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Secondary	Assessing the usefulness of biomarkers of hypoxic cerebral changes.	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	0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Secondary	Spinal cord model	To develop a hypoxic spinal cord model for use in future research looking into complex vascular surgery.	0 hour and 8, 11, 22 and 26 hours post hypoxic insult