Overview
Sponsor-declared trial summary
Cerebral amyloid angiopathy
To assess whether treatment with non-invasive vagus nerve stimulation (nVNS), low-sodium oxybate (LXB) or both interventions will increase the clearance of amyloid-beta (aβ) from the cerebral blood vessels, compared to pre-treatment, in patients with cerebral amyloid angiopathy (CAA) by stimulating the glymphatic syste…
Key facts
- Sponsor
- Academisch Ziekenhuis Leiden
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10], Phenomena and Processes [G] - Physiological processes [G07]
- Trial duration
- 27 Mar 2025 → ongoing
- Decision date (initial)
- 2024-04-08
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-506128-10-00
- WHO UTN
- U1111-1295-1113
- ClinicalTrials.gov
- NCT06421532
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Others
To assess whether treatment with non-invasive vagus nerve stimulation (nVNS), low-sodium oxybate (LXB) or both interventions will increase the clearance of amyloid-beta (aβ) from the cerebral blood vessels, compared to pre-treatment, in patients with cerebral amyloid angiopathy (CAA) by stimulating the glymphatic system.
Conditions and MedDRA coding
Cerebral amyloid angiopathy
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 4
- Patients with D-CAA with a proven APP mutation or a history of ≥1 lobar ICH and a positive family history for D-CAA in ≥1 first degree relative • Age ≥30 years old • ≤ 2 symptomatic ICH (occurrence of ICH at least > 1 year ago) or presence of ≥ 1 haemorrhagic marker (cortical superficial siderosis, cortical microbleeds) or non-haemorrhagic marker (white matter hyperintensities, microinfarcts, enlarged perivascular spaces, lobar lacunes). • When presymptomatic, patients are aware that they have D-CAA
- Probable sCAA according to the Modified Boston criteria 2.0 • Age ≥50 years old • ≤ 2 symptomatic ICH (occurrence of ICH at least > 1 year ago)
- Provisional CAA when the criteria for probable sCAA are not met due to presence of deep haemorrhagic lesions but there are mostly lobar MB and cSS present or a ratio of 10 times more lobar MB than deep MB without cSS. • Age ≥50 years old • ≤ 2 symptomatic ICH (occurrence of ICH at least > 1 year ago)
- Written informed consent
Exclusion criteria 7
- Modified Rankin Score ≥ 4
- A life expectancy of less than six months
- Pregnancy/breast feeding
- Contraindications for lumbar puncture
- Unwillingness to refrain from consuming ≤ 1 alcohol unit per day and not later than 8 pm.
- Contraindications for LXB and nVNS
- Contraindications for MRI 7T
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint will be the morning Aβ 40 and 42 levels in CSF before and after treatment. CSF will be obtained through a lumbar puncture before the intervention at 3 months and after the intervention at 6 months.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SUB14731MIG · Substance
- Active substance
- Sodium Oxybate
- Pharmaceutical form
- ORAL SOLUTION
- Route of administration
- ORAL
- Max daily dose
- 9.00
- Max total dose
- 756
- Max treatment duration
- 12 Week(s)
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Academisch Ziekenhuis Leiden
- Sponsor organisation
- Academisch Ziekenhuis Leiden
- Address
- Albinusdreef 2
- City
- Leiden
- Postcode
- 2333 ZA
- Country
- Netherlands
Scientific contact point
- Organisation
- Academisch Ziekenhuis Leiden
- Contact name
- S.E. Schriemer
Public contact point
- Organisation
- Academisch Ziekenhuis Leiden
- Contact name
- S.E. Schriemer
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 60 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2025-03-27 | 2025-03-27 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Onderzoeksprotocol 2023-506128-10-00_redacted | 4 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material for advertising | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information Clear-Brain and Cappricorn | 2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material gammaCore Sapphire | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material lumbar puncture | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material XYWAV | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC XYWAV | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2023-506128-10-00 for NL | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-12-08 | Netherlands | Acceptable 2024-04-02
|
2024-04-08 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-17 | Netherlands | Acceptable 2024-04-02
|
2024-12-17 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-08-20 | Netherlands | Acceptable 2024-04-02
|
2025-08-20 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-12-15 | Netherlands | Acceptable 2026-01-27
|
2026-01-30 |