BATMAN: Antibiotics Against Amyloid Angiopathy

Sponsor

Leiden University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT05680389

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cerebral Amyloid Angiopathy	Drug: Minocycline Drug: Placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 2, 2020

Anticipated Primary Completion Date :

Dec 2, 2023

Anticipated Study Completion Date :

Dec 2, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Minocycline 100 mg twice daily for 3 months	Drug: Minocycline 100 mg twice daily for 3 months
Placebo Comparator: Placebo twice daily for 3 months	Drug: Placebo twice daily for 3 months

Arm

Intervention/Treatment

Experimental: Minocycline

100 mg twice daily for 3 months

Drug: Minocycline

100 mg twice daily for 3 months

Placebo Comparator: Placebo

twice daily for 3 months

Drug: Placebo

twice daily for 3 months

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leiden University Medical Center	Leiden		Netherlands	2333ZA

Sponsors and Collaborators

Leiden University Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Marieke JH Wermer, MD, Prof Wermer, Leiden University Medical Center

ClinicalTrials.gov Identifier:

NCT05680389

Other Study ID Numbers:

P19.110
2019-004786-41

First Posted:

Jan 11, 2023

Last Update Posted:

Jan 11, 2023

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Cerebral Amyloid Angiopathy

Cerebral Amyloid Angiopathy, Familial

Amyloidosis

Minocycline

Study Results

No Results Posted as of Jan 11, 2023