Cerebral Amyloid Angiopathy
Conditions
Brief summary
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. Our aim is 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 persons with D-CAA (n=30) and sporadic-CAA (n=30).
Interventions
DRUGMinocycline
100 mg twice daily for 3 months
DRUGPlacebo
twice daily for 3 months
Sponsors
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years for D-CAA and age ≥55 years for sporadic-CAA * Probable-CAA according to the Modified-Boston-Criteria or genetically proven D-CAA * ≤ 2 ICH (occurrence of ICHs at least 1 year ago) and presence of ≥ 2 lobar microbleeds +/-cortical superficial siderosis * 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. In case of specific contra-indications for 7T a 3T will be made instead. - Specific contraindications for checkerboard 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 or thrombocytopenia (\<100). (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 outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF | 3 months | IL6, MCP-1, IBA-1, MMP2/9, and VEGF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| safety and tolerability of minocycline | 3 months | side effects and adverse events |
| progression of hemorrhagic markers on 7T MRI before and after treatment | 3 months | cSS, cortical microbleeds |
Countries
Netherlands
Contacts
Primary ContactSabine Voigt, BSc
Backup ContactMarieke Wermer, PhD
Outcome results
None listed