Feasibility of Improving Cerebral Autoregulation in Acute Intracerebral Haemorrhage

NCT03324321 | Completed DMC

• 1 other identifier: 0624
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Cerebral Haemodynamics; Carbon Dioxide; Cerebral Autoregulation

Outcome Measures

Primary Outcomes (4)

• Post Stroke Morbidity and Mortality

  Determined using Modified Rankin Scale 0 - No symptoms 1. \- No significant disability, despite symptoms; able to perform all usual duties and activities 2. \- Slight disability; unable to perform all previous activities but able to look after own affairs without assistance 3. \- Moderate disability; requires some help, but able to walk without assistance 4. \- Moderate severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. \- 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

Study Arms (1)

Hyperventilation Protocol

EXPERIMENTAL

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

Interventions

Hypocapnia via Hyperventilation Protocol OTHER

90 seconds of hyperventilation using a metronome to lower levels of -5mmHg and -10mmHg below baseline EtCO2

Hyperventilation Protocol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

University Hospitals of Leicester NHS Trust

Leicester, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 7762016 BACKGROUND

• 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.

  PMID: 26846864 BACKGROUND

• 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.

  PMID: 31500552 DERIVED

• 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.

  PMID: 29593024 DERIVED

MeSH Terms

Conditions

Stroke; Hemorrhage; Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intracranial Hemorrhages

Study Officials

• Thompson G Robinson, MD, FRCP

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-centre, prospective, before and after study

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: October 27, 2017
• Study Start: October 8, 2017
• Primary Completion: July 15, 2018
• Study Completion: July 15, 2018
• Last Updated: October 31, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)