Antibiotics Against Amyloid Angiopathy

Phase 1

Recruiting

• Conditions: Cerebral Amyloid Angiopathy
• Interventions: Drug: Placebo; Drug: Minocycline

• Registration Number: NCT05680389
• Lead Sponsor: Leiden University Medical Center

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-02
• Status Verified: 2022-12
• Study First Submitted: 2022-12-26
• Study First Submitted QC: 2022-12-26
• Last Update Submitted: 2022-12-26
• Study First Posted: 2023-01-11
• Last Update Posted: 2023-01-11
• Primary Completion: 2023-12-02
• Study Completion: 2023-12-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	twice daily for 3 months
Minocycline	Minocycline	100 mg twice daily for 3 months

Primary Outcome Measures

Name	Time	Method
inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF	3 months	IL6, MCP-1, IBA-1, MMP2/9, and VEGF

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands