The main objective will be to investigate whether treatment with nVNS on top of best medical practice in acute ischemic stroke patients results in smaller infarct volumes compared with the infarct volumes of patients not treated with nVNS.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be the infarct volume on MRI scan after 5 days of
patients treated with nVNS compared with those of patients not treated with
VNS.
Secondary outcome
Secondary endpoints will be:
o Feasibility and tolerability of nVNS
o Proportion of patients in whom <50% of the penumbra turned into ischemic core
on day 3
o Degree of blood-brain barrier leakage on day three measured with CTP
o NIHSS at day 5 or at day of discharge
o Clinical outcome (modified Rankin Scale, mRS) on day 90
o Occurrence of seizures, depression or headache in the first 90 days
Background summary
Stroke is the third most disabling disease world-wide and the second leading
cause of death. Secondary damage in the first few hours after ischemic stroke
contributes substantially to poor outcome. Currently, there are no therapies to
prevent secondary damage after ischemic stroke. Non-invasive vagus nerve
stimulation (nVNS) has been shown to reduce the extent of tissue injury and
functional deficit after ischemic stroke in rats. It is unknown whether nVNS
has the same effects in humans. Our hypothesis is that nVNS will reduce tissue
injury and prevent and reverse secondary damage after ischemic stroke.
Study objective
The main objective will be to investigate whether treatment with nVNS on top of
best medical practice in acute ischemic stroke patients results in smaller
infarct volumes compared with the infarct volumes of patients not treated with
nVNS.
Study design
The study will be a prospective randomized clinical trial with blinded outcome
assessment (PROBE design).
Intervention
Patients will be randomized by computer to nVNS with the gammaCore Sapphire* on
top of best medical practice versus best medical practice alone (including
intravenous thrombolysis and/or thrombectomy if indicated). If patients are
randomized to nVNS, two stimulations of two minutes each will be applied in the
neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be
applied every 8 hours over the next 5 days or until discharge, whichever occurs
first. The stimulation side in the neck will be the radiological side of the
stroke.
Study burden and risks
Invasive VNS (iVNS) has already been approved for treatment of depression and
refractory epilepsy and was safe in a small pilot study in ischemic stroke
patients. Non-invasive VNS (nVNS) has not yet been investigated in acute
ischemic stroke patients so the safety profile is not fully known. However,
based on results in earlier trials, we don*t expect major risks to be
associated with nVNS.
The following investigations will be done: all patients will undergo a CT/ CT
angiography (CTA)/ CT perfusion (CTP) scan on admission as part of standard
clinical care. On day 3 a CT/CTA/CTP scan will be repeated (for research
purposes). The risk related to this will be the radiation exposure
(approximately 13 mSv) and exposure to contrast agent. On day 5 or day of
discharge a non-contrast MRI scan will be performed (for research purposes)
which has minimal risks. On admission, day 5 or day of discharge, and after 90
days (by telephone) the modified Ranking Scale (mRS) will be assessed and a few
short questionnaires will be taken.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
Inclusion criteria
- Ischemic stroke
- NIHSS >=1
- Perfusion deficit on the admission CTP scan; the penumbra must comprise at
least 1/3 of the total ischemic area (ischemic core and penumbra)
- The infarct has to comprise the supratentorial region
- Treatment has to start <12 hours after stroke onset
- Patients or their representatives need to give their informed consent
Exclusion criteria
- Age below 18
- A life expectancy of less than three months
- mRS >2 prior to admission
- Contra-indication for contrast CT
- Contra-indications for VNS:
-> An active implantable medical device such as a pacemaker, deep brain
stimulator, or any implanted electronic device
-> Symptomatic stenosis or dissection of the carotid artery (in these patients
the other side will be stimulated unless a significant stenosis or dissection
on the other side is present as well)
-> Structural abnormality e.g. lymphadenopathy, previous surgery or abnormal
anatomy (in these patients the other side will be stimulated)
-> Metal cervical spine hardware or metallic implant near the stimulation site
-> Cervical vagotomy (in these patients the other side will be stimulated)
-> Pregnancy
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04050501 |
| CCMO | NL64702.058.18 |