Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH)
Primary Purpose
Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Hypocapnia via Hyperventilation Protocol
Sponsored by
About this trial
This is an interventional basic science trial for Stroke, Acute focused on measuring Cerebral Haemodynamics, Carbon Dioxide, Cerebral Autoregulation
Eligibility Criteria
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
Sites / Locations
- University Hospitals of Leicester NHS Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Hyperventilation Protocol
Arm Description
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.
Outcomes
Primary Outcome Measures
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
The percentage of recruited subjects able to comply with the full measurement protocol
The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03324321
First Posted
October 9, 2017
Last Updated
October 30, 2018
Sponsor
University of Leicester
1. Study Identification
Unique Protocol Identification Number
NCT03324321
Brief Title
Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage
Acronym
BREATHE-ICH
Official Title
Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) Study
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 8, 2017 (Actual)
Primary Completion Date
July 15, 2018 (Actual)
Study Completion Date
July 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Leicester
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Acute, Hemorrhage, Cerebral Brain Hemorrhage, Blood Pressure
Keywords
Cerebral Haemodynamics, Carbon Dioxide, Cerebral Autoregulation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single-centre, prospective, before and after study
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Hyperventilation Protocol
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Hypocapnia via Hyperventilation Protocol
Intervention Description
90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2
Primary Outcome Measure Information:
Title
Post Stroke Morbidity and Mortality
Description
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
Time Frame
14 days
Title
The percentage of recruited subjects able to comply with the full measurement protocol
Time Frame
14 days
Title
The percentage of measurements rejected because of aspects related to data quality during the analysis protocol, with recorded reasons
Time Frame
14 days
Title
The percentage of recruited subjects in whom values for the following cerebral haemodynamic parameters can be derived
Description
% 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
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thompson G Robinson, MD, FRCP
Organizational Affiliation
University of Leicester
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals of Leicester NHS Trust
City
Leicester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
7762016
Citation
Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static and dynamic cerebral autoregulation measurements. Stroke. 1995 Jun;26(6):1014-9. doi: 10.1161/01.str.26.6.1014.
Results Reference
background
PubMed Identifier
26846864
Citation
Ma H, Guo ZN, Liu J, Xing Y, Zhao R, Yang Y. Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage. Stroke. 2016 Mar;47(3):674-81. doi: 10.1161/STROKEAHA.115.011453. Epub 2016 Feb 4.
Results Reference
background
PubMed Identifier
31500552
Citation
Minhas JS, Panerai RB, Swienton D, Robinson TG. Feasibility of improving cerebral autoregulation in acute intracerebral hemorrhage (BREATHE-ICH) study: Results from an experimental interventional study. Int J Stroke. 2020 Aug;15(6):627-637. doi: 10.1177/1747493019873690. Epub 2019 Sep 9.
Results Reference
derived
PubMed Identifier
29593024
Citation
Minhas JS, Panerai RB, Robinson TG. Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage (BREATHE-ICH) study: a protocol for an experimental interventional study. BMJ Open. 2018 Mar 27;8(3):e020758. doi: 10.1136/bmjopen-2017-020758.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
Funder
Available IPD/Information URL
http://dunhillmedical.org.uk/
Available IPD/Information Comments
Dunhill RTF Grant (RTF97/0117)
Learn more about this trial
Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage
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