Antibiotics Against Amyloid Angiopathy

NCT05680389 | Unknown Phase 1

• 2 other identifiers: P19.1102019-004786-41
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Cerebral Amyloid Angiopathy

Outcome Measures

Primary Outcomes (1)

• inflammatory, vessel integrity and gelatinase pathway associated biomarkers in CSF

  IL6, MCP-1, IBA-1, MMP2/9, and VEGF

  3 months

Secondary Outcomes (2)

• safety and tolerability of minocycline

  3 months

• progression of hemorrhagic markers on 7T MRI before and after treatment

  3 months

Study Arms (2)

Minocycline

EXPERIMENTAL

100 mg twice daily for 3 months

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

twice daily for 3 months

Drug: Placebo

Interventions

Minocycline DRUG

100 mg twice daily for 3 months

Minocycline

Placebo DRUG

twice daily for 3 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333ZA, Netherlands

RECRUITING

Related Publications (1)

• Voigt S, Koemans EA, Rasing I, van Etten ES, Terwindt GM, Baas F, Kaushik K, van Es ACGM, van Buchem MA, van Osch MJP, van Walderveen MAA, Klijn CJM, Verbeek MM, van der Weerd L, Wermer MJH. Minocycline for sporadic and hereditary cerebral amyloid angiopathy (BATMAN): study protocol for a placebo-controlled randomized double-blind trial. Trials. 2023 Jun 5;24(1):378. doi: 10.1186/s13063-023-07371-4.

  PMID: 37277877 DERIVED

MeSH Terms

Conditions

Cerebral Amyloid Angiopathy

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Cerebral Arterial Diseases; Intracranial Arterial Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Central Study Contacts

Sabine Voigt, BSc

CONTACT

+31715261825; BATMAN@lumc.nl

Marieke Wermer, PhD

CONTACT

BATMAN@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Wermer

Study Record Dates

• First Submitted: December 26, 2022
• First Posted: January 11, 2023
• Study Start: December 2, 2020
• Primary Completion: December 2, 2023
• Study Completion: December 2, 2023
• Last Updated: January 11, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)