To prove in a randomized clinical trial in a translational setting that minocycline treatment (duration 3 months) can decrease markers of neuroinflammation and the gelatinase pathway in the cerebrospinal fluid (CSF) of patients with HCHWA-D (n=30)…
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Markers of neuroinflammation and the gelatinase pathway in the CSF.
Secondary outcome
The effect of minocycline on microvascular CAA markers on 7 Tesla MRI.
Background summary
Cerebral Amyloid Angiopathy (CAA) is a disease caused by accumulation of the
protein amyloid-beta in the leptomeningeal arteries, cortical arterioles and
capillaries of the brain. It is one of the major causes of ICH and vascular
dementia in the elderly. Approximately 60% of all lobar (cortical) ICHs are CAA
related.1 Most CAA cases are sporadic but a few familial forms exist. Around
the Dutch village Katwijk (near Leiden) several families suffer from hereditary
Dutch type Cerebral Amyloid Angiopathy (D-CAA), also known as: Hereditary
Cerebral Hemorrhage With Amyloidosis - Dutch type (HCHWA-D), an autosomal
dominant familial form of CAA. D-CAA, like sporadic-CAA is characterized by
recurrent ICH and dementia, although we showed that its disease course is more
aggressive.2 Currently, there is no treatment for D-CAA or sporadic CAA.
Presence of amyloid-beta induces a chronic state of cerebral inflammation by
activating reactive astrocytes, microglia and pro-inflammatory substances.3, 4
We will perform a randomized clinical trial with minocycline. Minocycline is an
antibiotic of the tetracycline family and known to modulate inflammation,
gelatinase activity and angiogenesis, which we know are central mechanisms in
CAA-pathology.
Study objective
To prove in a randomized clinical trial in a translational setting that
minocycline treatment (duration 3 months) can decrease markers of
neuroinflammation and the gelatinase pathway in the cerebrospinal fluid (CSF)
of patients with HCHWA-D (n=30) and sporadic-CAA (n=30).
Study design
The study design is a randomized double-blind placebo-controlled trial.
Intervention
60 patients will be randomized and receive either placebo or minocycline
treatment (15 sCAA placebo, 15 sCAA minocycline, 15 D-CAA placebo and 15 D-CAA
minocycline).
Study burden and risks
Blood withdrawal and lumbar punctures are routine procedures at the Department
of Neurology. Lumbar puncture will be performed by experienced physicians. We
will use atraumatic spinal needles to reduce the risk of post-lumbar puncture
headache. Patients will be informed extensively about the potential risks of
these procedures, after which written informed consent will be obtained. The
risks of MRI are minimal (risk of everyday life), because there are no
consequences to the health of the participant. Contra-indications will be
carefully investigated per subject, burden will be kept at a minimum by using
short protocols. There is no direct benefit for the patients except for more
insight in the possible effect of minocycline on CAA.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
- Age >=18 years for HCHWA-D and age >=50 years for sporadic-CAA
- Probable-CAA according to the Boston criteria 2.0, or genetically proven
D-CAA
- <= 2 ICH (occurrence of ICHs at least 1 year ago) and presence of >= 2 lobar
microbleeds +/-cortical superficial siderosis
- Presence of deep microbleeds is allowed if
- There is presence of cortical superficial siderosis, or
- >=10 lobar microbleeds are present for every deep microbleed
- Written informed consent
Exclusion criteria
- Previous allergic reactions to minocycline
- Modified Rankin Score >=3
- Contraindications, such as:
- 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.
- Specific contraindications for fMRI: seizure within prior year,
photosensitive epilepsy, noncorrectable visual impairment.
- 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, a coagulopathy including use of anti-coagulant
drugs (INR>=1.8) or thrombocytopenia (<40).
(Use of acetylsalicylic acid, NSAIDs, COX2 inhibitors or low-molecular-weight
heparin are no contraindications for lumbar puncture.)
- Pregnancy/breast feeding
- Liver/renal failure
- Use of antibiotics <1 month
- SLE or other diseases known to generate inflammatory responses
- Previous/current/planned use of retinoids (since this is related to
increasing risk of increased intracranial pressure)
- Current use of anaesthetics like methoxyflurane, agents inhibiting
peristalsis, barbiturates, carbamazepine or fenytoïne
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 |
|---|---|
| EudraCT | EUCTR2019-004786-41-NL |
| CCMO | NL71513.058.20 |