Antibiotics Against Amyloid Angiopathy

Study Overview
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Brief Summary
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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).

Official Title
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Placebo-controlled, Randomized, Double-blind Study of Minocycline for Sporadic and Hereditary Cerebral Amyloid Angiopathy

Conditions
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Cerebral Amyloid Angiopathy

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minocycline<br>100 mg twice daily for 3 months | Drug: Minocycline<br>* 100 mg twice daily for 3 months<br>|
| Placebo Comparator: Placebo<br>twice daily for 3 months | Drug: Placebo<br>* twice daily for 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF | IL6, MCP-1, IBA-1, MMP2/9, and VEGF | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of minocycline | side effects and adverse events | 3 months | 
| progression of hemorrhagic markers on 7T MRI before and after treatment | cSS, cortical microbleeds | 3 months |