High Altitude Cerebral EdemaPhase 1D4HNCT03341676
Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)
A Phase 1 study testing Dexamethasone in people with High Altitude Cerebral Edema, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- High Altitude Cerebral Edema
- What is being tested?
- Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Jan 2019to 31 Aug 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Coventry and Warwickshire NHS Trust
Coventry, West Midlands, CV2 2DX
About this study
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.
Read the 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
- Being tested
- Dexamethasone, Placebo
- Medical subject headings
- Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Dexamethasone 3.3 mg/mL solution for injection
PlaceboDrug
Sodium Chloride 0.9% w/v solution for injection
| Study group | Role | What they receive |
|---|---|---|
| Dexamethasone | Experimental | 8ml IV 3.3mg/mL dexamethasone Receives: Drug: Dexamethasone |
| Placebo | Placebo comparator | 8ml IV 0.9% w/v saline Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Secondary outcomes (3)
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
Measured: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult
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
Measured: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Spinal cord model
To develop a hypoxic spinal cord model for use in future research looking into complex vascular surgery.
Measured: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2017
- Study start14 Jan 2019
- Primary completion31 Aug 2023
- Study completion31 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for High Altitude Cerebral EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomised controlled trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christopher Imray, PhD MBBS, Principal investigator, University Hospital Coventry and Warwickshire NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03341676
- Sponsor's protocol ID
- CI175716
- Acronym
- D4H
- Status last verified
- Jun 2024
- First submitted
- 9 Mar 2017
- Last updated
- 18 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared with other researchers
Publications
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.
PubMed 31651350
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spectroscopic and Diffusion Weighted Analysis of the Effects of Dexamethasone on High Altitude Cerebral Oedema (HACE)
- ClinicalTrials.gov ID
- NCT03341676
- Acronym / sponsor ID
- D4H / CI175716
- Conditions
- High Altitude Cerebral Edema
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Hospitals Coventry and Warwickshire NHS TrustUniversity, hospital or other
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 31 Aug 2023 (actual)
- First posted
- 14 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| Dexamethasone | Experimental | Drug: Dexamethasone8ml IV 3.3mg/mL dexamethasone |
| Placebo | Placebo comparator | Drug: Placebo8ml IV 0.9% w/v saline |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneDexamethasone 3.3 mg/mL solution for injection | Drug | Dexamethasone |
| PlaceboSodium Chloride 0.9% w/v solution for injection | Drug | Placebo |
Primary outcome
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
3 secondary outcomes
Primary blood brain barrier breakdown in hypoxic cytotoxic oedema
Time frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult
Assessing the usefulness of biomarkers of hypoxic cerebral changes.
Time frame: 0 hour and 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2024.
- Derived from this study: PubMed 31651350Fisher 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.
- Individual participant dataSharing planned: No. Individual participant data will not be shared with other researchers
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christopher Imray, PhD MBBS principal investigator
University Hospital Coventry and Warwickshire NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexamethasone in people with High Altitude Cerebral Edema, run by University Hospitals Coventry and Warwickshire NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in oedematous changes in the brain and spinal cord (time frame: 0 hour and 8, 11, 22 and 26 hours post hypoxic insult). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03341676, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2024.