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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Blood Pressure; Stroke, Acute; Cerebral Brain Hemorrhage
• Intervention / Treatment: Other: Hypocapnia via Hyperventilation Protocol

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Leicester, United Kingdom
    • University Hospitals of Leicester NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hyperventilation Protocol; 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; 90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2

What is the study measuring?

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) periodsAutoregulation index	14 days

Collaborators and Investigators

• Sponsor: University of Leicester
• Investigators: Principal Investigator: Thompson G Robinson, MD, FRCP, University of Leicester

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2017
• Primary Completion (Actual): July 15, 2018
• Study Completion (Actual): July 15, 2018

Study Registration Dates

• First Submitted: October 9, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Carbon Dioxide; Cerebral Autoregulation; Cerebral Haemodynamics
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Hemorrhage; Intracranial Hemorrhages; Cerebral Hemorrhage
• Other Study ID Numbers: 0624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Study Data/Documents

1. Funder
   Information comments: Dunhill RTF Grant (RTF97/0117)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No