Clear-Brain: A partial randomised clinical trial investigating stimulation of the glymphatic system by either deepening sleep with lower-sodium oxybate or inhibiting cortical spreading depressions with non-invasive vagus nerve stimulation, or both, in patients with Cerebral Amyloid Angiopathy (CAA).
- Conditions
- CAACerebral Amyloid Angiopathy10007963
- Registration Number
- NL-OMON56712
- Lead Sponsor
- eids Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 60
1. Patients with D-CAA with a proven APP mutation or a history of >=1 lobar ICH
and a positive family history for D-CAA in >=1 first degree relative - Age >=30
years old - <= 2 symptomatic ICH (occurrence of ICH at least > 1 year ago) or
presence of >= 1 haemorrhagic marker (cortical superficial siderosis, cortical
microbleeds) or non-haemorrhagic marker (white matter hyperintensities,
microinfarcts, enlarged perivascular spaces, lobar lacunes). - When
presymptomatic, patients are aware that they have D-CAA 2. Probable sCAA
according to the Modified Boston criteria 2.0 - Age >=50 years old - <= 2
symptomatic ICH (occurrence of ICH at least > 1 year ago) 3. Provisional CAA
when the criteria for probable sCAA are not met due to presence of deep
haemorrhagic lesions but there are mostly lobar MB and cSS present or a ratio
of 10 times more lobar MB than deep MB without cSS. - Age >=50 years old - <= 2
symptomatic ICH 4. Written informed consent
A patient who meets any of the following criteria will be excluded from
participation in this study: - Modified Rankin Score >= 4 - A life expectancy of
less than six months - Pregnancy/breast feeding - Contraindications for lumbar
puncture - Contraindications for nVNS and LXB - Unwillingness to refrain from
consuming <= 1 alcohol unit per day and not later than 8 pm. Specific
contraindications for certain measurements or intervention: 1.
Contraindications for using LXB: - Sleep apnea; patients will be screened with
respiratory polygraphy before inclusion and screening by questionnaire during
intervention with LXB. - Restless legs (RLS) needing active treatment with RLS
medication. - Currently suffering from severe depression and using medication
or receiving cognitive therapy. - Porphyria - Succinic semialdehyde
dehydrogenase (SSADH-)deficiency - Use of opiates, barbiturates, sedatives
(dexmedetomidine, temazepam, oxazepam, midazolam) - Use certain medication
before inclusion: * When benzodiazepine is used: a two nights washout before
the intervention (T3) will be started, is needed. * When LXB is used before
inclusion: one week washout before inclusion and no use of LXB during inclusion
except for the intervention dose. 2. Contraindications for lumbar puncture: -
Compression of the spinal cord - Signs and symptoms of increased intracranial
pressure - Local infections of the skin at the puncture site - Coagulopathy or
thrombocytopenia (<100) - (Use of acetylsalicylic acid, NSAIDs, COX2 inhibitors
or low-molecular-weight heparin are no contraindications for lumbar puncture.)
3. Contraindications for nVNS: - An active implantable medical device such as a
pacemaker, deep brain stimulator, or any implanted electronic device. - A
recent (< 1 month) brain infarction or transient ischemic attack due to a
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). - If someone knows to have a 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) 4. Contraindications for 7T
MRI as determined by the 7Tesla safety committee. Examples of possible
contra-indications are: - Claustrophobia - Pacemakers and defibrillators -
Nerve stimulators - Intracranial clips - Intraorbital or intraocular metallic
fragments - Cochlear implants - Ferromagnetic implants - Hydrocephalus pump -
Intra-uterine device - Permanent make-up - Tattoos above the shoulders 5.
Specific contraindications for checkerboard fMRI: - Seizure within prior year -
Photosensitive epilepsy - Non-correctable visual impairment
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint will be the morning Aβ 40 and 42 levels in CSF before and<br /><br>after treatment. CSF will be obtained through a lumbar puncture before the<br /><br>intervention at 3 months and after the intervention at 6 months.</p><br>
- Secondary Outcome Measures
Name Time Method