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

NCT ID: NCT03341676

Last Updated: 2024-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-14
• Study Completion Date: 2023-08-31

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.

Conditions

High Altitude Cerebral Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dexamethasone

8ml IV 3.3mg/mL dexamethasone

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Dexamethasone 3.3 mg/mL solution for injection

Placebo

8ml IV 0.9% w/v saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium Chloride 0.9% w/v solution for injection

Interventions

Dexamethasone

Dexamethasone 3.3 mg/mL solution for injection

Intervention Type: DRUG

Placebo

Sodium Chloride 0.9% w/v solution for injection

Intervention Type: DRUG

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospitals Coventry and Warwickshire NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Imray, PhD MBBS

Role: PRINCIPAL_INVESTIGATOR

University Hospital Coventry and Warwickshire NHS Trust

Locations

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, West Midlands, United Kingdom

Countries

United Kingdom

References

Fisher O, Benson RA, Wayte S, Kimani PK, Hutchinson C, Imray CHE. Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema: protocol for a pilot study. Trials. 2019 Oct 24;20(1):604. doi: 10.1186/s13063-019-3681-0.

Reference Type: DERIVED

PMID: 31651350 (View on PubMed)

Other Identifiers

CI175716

Identifier Type: -

Identifier Source: org_study_id