Antibiotics Against Amyloid Angiopathy

Cerebral Amyloid Angiopathy Clinical Trial

— BATMAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05680389
• Other study ID #: P19.110
• Secondary ID: 2019-004786-41
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2, 2020
• Est. completion date: December 2, 2023

Study information

• Verified date: December 2022
• Source: Leiden University Medical Center
• Contact: Sabine Voigt, BSc
• Phone: +31715261825
• Email: BATMAN[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2, 2023
• Est. primary completion date: December 2, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Cerebral Amyloid Angiopathy

Intervention

Drug:
• Minocycline
100 mg twice daily for 3 months
• Placebo
twice daily for 3 months

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF	IL6, MCP-1, IBA-1, MMP2/9, and VEGF	3 months
Secondary	safety and tolerability of minocycline	side effects and adverse events	3 months
Secondary	progression of hemorrhagic markers on 7T MRI before and after treatment	cSS, cortical microbleeds	3 months