Clinical trial NCT05680389: Antibiotics Against Amyloid Angiopathy
Official title: Placebo-controlled, Randomized, Double-blind Study of Minocycline for Sporadic and Hereditary Cerebral Amyloid Angiopathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Cerebral Amyloid Angiopathy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2023-01-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF
timeFrame: 3 months
Secondary outcomes:
measure: safety and tolerability of minocycline
timeFrame: 3 months
measure: progression of hemorrhagic markers on 7T MRI before and after treatment
timeFrame: 3 months
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
References: