Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03886129 |
| Other study ID # |
0694 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 16, 2019 |
| Est. completion date |
March 31, 2021 |
Study information
| Verified date |
May 2021 |
| Source |
University of Leicester |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Adequate brain blood flow is essential for brain survival and function. Brain blood flow is
kept relatively constant by a process called cerebral autoregulation (CA). CA is impaired in
various diseases including head injury, diabetes, Alzheimer's, pre-eclampsia and stroke. In
stroke, impaired CA is associated with poor outcomes. A transient ischaemic attack (TIA) is
the same as a stroke, except the symptoms only last for a short amount of time and resolve
spontaneously. TIAs are sometimes called mini-strokes and are a major warning sign of
strokes. There have been lots of studies of CA in stroke, but very few studies of CA in TIA.
Brain blood flow and CA can be studied non-invasively with Transcranial Doppler ultrasound
(TCD).
Study aim: To investigate whether CA is impaired in patients with TIA
20 patients with acute TIA (within 7 days), and 20 healthy controls will be recruited from
the specialist TIA clinic at University Hospitals of Leicester NHS Trust. Participants will
be eligible if they are aged over 18 and can consent to participate. They won't be able to
participate if they have severe heart failure, an irregular heartbeat, blocked neck blood
vessels, severe breathing problems, or if they are pregnant.
Participants will undergo an assessment of brain blood flow using TCD, during which their
heart rate, breathing and blood pressure will also be monitored. During the assessment
participants will sit quietly before being asked to stand and then complete a squat-stand
manoeuvre in time with a computer sequence. The research visit will take approximately 90
minutes, the assessment itself will take approximately 1 hour and participants only need to
attend once.
Description:
Adequate brain blood flow is essential for brain survival and function. Brain blood flow is
kept relatively constant by a process called cerebral autoregulation (CA). CA is impaired in
various diseases including head injury, diabetes, Alzheimer's dementia, pre-eclampsia and
stroke. In stroke, impaired CA is associated with early deterioration and the need for
emergency surgery to relieve brain swelling. Impaired CA in stroke has also been shown to be
related to stroke severity and functional outcomes.
A transient ischaemic attack (TIA), also known as a mini-stroke, is the same as a stroke,
except that the symptoms only last for a short amount of time and resolve spontaneously.
Every year at least 46,000 people in the United Kingdom have a TIA for the first time. TIA is
strongly predictive of future stroke, and the risk is heavily front loaded; one in 12 people
will have a full stroke within a week of having a TIA. Prompt assessment following a TIA
helps to reduce this risk. Indeed, urgently investigating and treating people who have a TIA
in a specialist clinic reduces their risk of another stroke by 80%. However, some people will
unfortunately go on to have a stroke despite this, and the reasons for this are not always
clear. Furthermore, although TIAs fully resolve, around 70% of people report long term
effects after a TIA including memory loss, tiredness and low mood.
Brain blood flow and CA can be studied using ultrasound which is passed through the skull,
known as Transcranial Doppler ultrasonography (or TCD). Ultrasound has been tried and tested
over many years and unlike CT or MRI scans, does not use any radiation. It is also
inexpensive, and can be used in patients with pacemakers.
In order to study CA, it is necessary to see what happens to brain blood flow when there are
changes in blood pressure. Although some people have natural ups and downs in their blood
pressure at rest, these are not always big enough to study brain blood flow effectively.
Larger changes in blood pressure can be induced with challenges such as placing hands in ice
cold water, or inflating large blood pressure cuffs on the tops of the legs before suddenly
releasing them. These can be uncomfortable for participants. More recently, squat-stand
manoeuvres (SSMs) have also been shown to produce large changes in blood pressure. They have
been shown to be safe and well tolerated in various populations including heart transplant
recipients, young and old healthy controls, and patients with Alzheimer's dementia. It has
recently been shown that reliable CA data can be obtained from as few as three SSMs.
There have been lots of studies of CA in stroke, but very few studies of CA in TIA. The small
studies that are available are conflicting about whether brain blood flow and CA are altered
in TIA. The aim of this study is therefore to investigate whether CA is impaired in patients
with TIA. If CA is impaired in patients with TIA, then it may be possible to identify
abnormalities in brain blood flow that can help predict who might go on to suffer a stroke,
or suffer other complications.
This is a single-centre, case-control study being undertaken at the University Hospitals of
Leicester NHS Trust.
Once ethical approvals, and all relevant sponsorship and regulatory approvals, are in place
20 patients with acute TIA (within 7 days of event), and 20 healthy controls will be
recruited from the specialist TIA clinic at University Hospitals of Leicester NHS Trust.
Medical records will be reviewed by the direct care team to ensure participants meet the
inclusion and exclusion criteria. Participants will be eligible if they are aged over 18 and
can consent to participate. They won't be able to participate if they have severe heart
failure, an irregular heartbeat, blocked neck blood vessels, severe breathing problems, or if
they are pregnant. Eligibility screening will only be undertaken by the direct clinical care
team for potential participants. Participants will be approached at their clinical
consultation in the specialist TIA clinic by consultants, registrars or specialist nurses to
determine study interest prior to referral to the researcher and provision of study specific
information. A poster advertising the study will be displayed in the TIA clinic waiting room.
Both participants with TIA, and healthy controls (those without a diagnosis of TIA) will be
recruited from the clinic. Healthy spouses, friends or partners of patients with TIA will be
asked if they would like to participate in the study as a healthy control subject.
Participants who meet the inclusion criteria will attend the Leicester Cerebral Haemodynamics
in Ageing and Stroke Medicine (CHiASM) research laboratory. Formal, written consent will be
obtained, followed by an ultrasound check of their brain blood flow. In approximately 5-37%
of patients we are not able to perform the ultrasound procedure as the blood vessels cannot
be seen through the skull, which would prevent them from enrolling into the study. Following
this, background information on age, sex, medical conditions, and medication use will be
collected. The Edinburgh handedness inventory will be completed to determine left or right
hand dominance, and the office of National Statistics questionnaire to determine ethnicity.
Participants will then undergo an assessment of brain blood flow using TCD, with two small
ultrasound probes held in place on the temples with a customised headframe. During the
assessment, heart rate, breathing and blood pressure will also be monitored. Heart rate will
be monitored using a 3 lead ECG, blood pressure will be monitored using a cuff on the finger
with the arm supported in a sling, and breathing will be monitored using nasal tubes. The
assessment will consist of three recordings. Firstly, participants will sit quietly for 5
minutes. Next, they will be asked to sit quietly for one minute before standing and remaining
standing for 5 minutes. Lastly, they will be asked to stand and then complete a squat-stand
manoeuvre in time with a computer sequence. A tilt sensor will be attached to the thigh to
measure the efficiency and angle of the squatting motion. The squat-stand manoeuvre will
consist of 15 squats and participants will be informed that they should try and complete all
15 squats if possible. However, if they wish to stop before this, they should make the
investigator aware during a standing period and remain standing for 90 seconds before the
equipment is disconnected.
The research visit will take approximately 90 minutes, the assessment itself will take
approximately 1 hour and participants only need to attend once.
