Cerebral Amyloid Angiopathy (CAA) Cerebral Amyloid Angiopathy (CAA)
Conditions
Interventions
60 Persons will receive enhancement of the glymphatic system by using LXB, nVNS or both interventions with as enrichment randomisation (10 D-CAA LXB, 10 D-CAA nVNS, 10 D-CAA both, 10 sCAA LXB, 10 sCAA
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 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 - 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 - 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 -
Exclusion criteria
Exclusion criteria: 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. - More than one period with clinical inflammation confirmed with MRI regarding CAA-related inflammation (CAA-ri) or less than 6 months stable after the last prednisone treatment for CAA-ri. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Morning Aß 40 and 42 levels in cerebrospinal fluid (CSF) before and after intervention. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcomes are difference in morning Aß 40 and 42 levels in CSF before and after intervention between groups, disease progression measured by (non-)haemorrhagic imaging markers with 7T MRI and the CAA-burden score. | — |
Countries
Netherlands
Contacts
Public ContactS.E. Schriemer
Leids Universitair Medisch Centrum
Outcome results
None listed