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

NCT03341676 | Completed Phase 1 DMC

• 1 other identifier: CI175716
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

High Altitude Cerebral Edema

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Primary blood brain barrier breakdown in hypoxic cytotoxic oedema

  0 hour and 8, 11, 22 and 26 hours post hypoxic insult

• Assessing the usefulness of biomarkers of hypoxic cerebral changes.

  0 hour and 8, 11, 22 and 26 hours post hypoxic insult

• Spinal cord model

  0 hour and 8, 11, 22 and 26 hours post hypoxic insult

Study Arms (2)

Dexamethasone

EXPERIMENTAL

8ml IV 3.3mg/mL dexamethasone

Drug: Dexamethasone

Placebo

PLACEBO COMPARATOR

8ml IV 0.9% w/v saline

Drug: Placebo

Interventions

Dexamethasone DRUG

Dexamethasone 3.3 mg/mL solution for injection

Dexamethasone

Placebo DRUG

Sodium Chloride 0.9% w/v solution for injection

Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospitals Coventry and Warwickshire NHS Trust: lead

Study Sites (1)

University Hospitals Coventry and Warwickshire NHS Trust

Coventry, West Midlands, CV2 2DX, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31651350 DERIVED

MeSH Terms

Conditions

Altitude Sickness

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Christopher Imray, PhD MBBS

  University Hospital Coventry and Warwickshire NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, Investigator supervising the visit and the Outcome Assessor will be blinded to the treatment allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomised controlled trial

Study Record Dates

• First Submitted: March 9, 2017
• First Posted: November 14, 2017
• Study Start: January 14, 2019
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: June 18, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)