Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage

Study Overview
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Brief Summary
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In the UK, 23,000 (15%) of the 150,000 people who suffer a stroke each year have bleeding in the brain, also referred to as acute intracerebral haemorrhage (ICH). An Autoregulation Index (ARI) can be assigned between 0 and 9 (0 being poor and 9 being the most efficient CA observed) to gauge how good the control over blood flow is at a given time. Dynamic CA (dCA) is a measure of the response of cerebral blood flow (CBF) to rapid changes in blood pressure (BP), and several key studies have shown impaired dCA post-acute ICH. The most recent study demonstrated that dCA impairment lasts up to 12 days. This is particularly important to understand, since our preliminary work has recently shown that changes in carbon dioxide using simple breathing exercises can improve Autoregulation. Unfortunately, there are limited non-pharmacological management options and significant opportunities to improve patient outcome in ICH. The proposed study addresses this area, by investigating whether a simple breathing exercise in survivors of ICH is safe, feasible and effective in reducing brain injury by improving cerebral autoregulation.

Official Title
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Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) Study

Conditions
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Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage, Blood Pressure

Intervention / Treatment
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* Other: Hypocapnia via Hyperventilation Protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of a haemorrhagic stroke within 48 hours of onset (for patients waking with a stroke, time of onset will be taken to be the time when the patient was last asymptomatic) Able and willing to give informed consent Male or female, aged 18 years or above Able (in the Investigator's opinion) and willing to comply with all study requirements Willing to allow his or her General Practitioner (GP) to be notified of participation in the study Exclusion Criteria: Male or Female, aged under 18 years Significant previous airways disease (formal diagnosis of moderate or severe airways disease and having treatment for this respiratory condition - via inhalers or specialist input) Unable (in the Investigator's opinion) or unwilling to comply with any study requirements Female participants who are pregnant, lactating or planning pregnancy during the course of the study Clinical diagnosis of stroke greater than 48 hours from onset Having had a resolved transient ischaemic attack (TIA) (i.e. neurological symptoms completely resolved upon hospital presentation) Co-morbidity with anticipated life expectancy less than 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Single-centre, prospective, before and after study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperventilation Protocol<br>This will involve sustained periods of 90-seconds of hyperventilation at two levels (-5mmHg and -10mmHg below baseline EtCO2) to a maximum lower level threshold of EtCO2 24mmHg/CBFV 33cm/s regulated using a metronome. Two-minute washout periods of normal respiration will be allowed between successive measurements. Each incremental reduction in pCO2 will be repeated on two occasions during the same session. Further assessments will be conducted 10-14 days following baseline assessments. | Other: Hypocapnia via Hyperventilation Protocol<br>* 90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post Stroke Morbidity and Mortality | Determined using Modified Rankin Scale 0 - No symptoms - No significant disability, despite symptoms; able to perform all usual duties and activities - Slight disability; unable to perform all previous activities but able to look after own affairs without assistance - Moderate disability; requires some help, but able to walk without assistance - Moderate severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance - Severe disability; bedridden, incontinent, and requires constant care 6- Death | 14 days | 
| The percentage of recruited subjects able to comply with the full measurement protocol |  | 14 days | 
| The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons |  | 14 days | 
| The percentage of recruited subjects in whom values for the following cerebral haemodynamic parameters can be derived | % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods Autoregulation index % change in CBFv at baseline and in response to a hyperventilation manoeuvre in the acute (<48 hours) and sub-acute (10 to 14 days) periods Autoregulation index | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Haemodynamics, Carbon Dioxide, Cerebral Autoregulation