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Can deep sleep or nerve stimulation flush toxic proteins from the brain?

NCT ID NCT06421532

What the study statuses mean

This study's is highlighted.

Recruitment status, easiest to join first

Recruiting now
This trial is taking on new participants right now.
Not yet recruiting
Registered, but not yet taking participants.
By invitation only This study
Not open to general applications. Only people the study team invites can take part.
Paused
Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
Expanded access (paused)
Not a trial. The treatment can normally be requested outside a study, but is unavailable right now.
Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

When the status isn't known

Details not published
The full record has not been published yet, so there is little to show here.
Status unknown
This status has not been confirmed recently, so it may be out of date.

First seen Jun 26, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This Phase 2 trial tests whether a sleep-deepening drug (lower-sodium oxybate) or a nerve-stimulating device (non-invasive vagus nerve stimulation), or both, can help clear amyloid-beta protein from the brain in people with cerebral amyloid angiopathy (CAA). Sixty participants will be randomly assigned to one of the treatments for three months. The main goal is to measure changes in amyloid levels in spinal fluid, with brain scans used to track disease progression.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
lower-sodium oxybate (XYWAV) and non-invasive vagus nerve stimulation (gammaCore Sapphire)
What this could lead to
If successful, this could point toward a new way to clear harmful protein buildup in the brain and slow disease progression in cerebral amyloid angiopathy.
What could go wrong
This is a small, early-phase trial (60 people) testing a biomarker, not a clinical outcome. The interventions may not improve symptoms or prevent bleeding, and side effects from the drug or device are possible.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 60 people

The number the study aims to enrol. It can still change while the study runs.

Started

Mar 2025

Expected to finish

Sep 2027

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

30 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patients with D-CAA with a proven amyloid precursor protein (APP) mutation or a history of ≥1 lobar intracerebral haemorrhage (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, cerebral microbleeds) or non-haemorrhagic marker (white matter hyperintensities, enlarged perivascular spaces). * When presymptomatic, patients are aware that they have D-CAA * Probable sporadic CAA (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 microbleeds (MBs) and cortical superficial siderosis (cSS) present or a ratio of 10 times more lobar MBs than deep MBs without cSS. * Age ≥50 years old * ≤ 2 symptomatic ICH (occurrence of ICH at least \> 1 year ago) * Participants able to read and understand the patient information folder and who freely provide written informed consent Exclusion Criteria: * 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, during the intervention period. Contraindications for using LXB: * Sleep apnea; patients will be screened with respiratory polygraphy before inclusion and screening by questionnaire during intervention with LXB. * Restless legs (RLS) needing active treatment with RLS medication. * Currently suffering from severe depression and using medication or receiving cognitive therapy. * Porphyria * Succinic semialdehyde dehydrogenase (SSADH-)deficiency * Use of opiates, barbiturates, sedatives (dexmedetomidine, temazepam, oxazepam, midazolam) * Use certain medication before inclusion: * When benzodiazepine is used: a two nights washout before the intervention (T3) will be started, is needed. * When LXB or SXB is used before inclusion: one week washout before inclusion and no use of LXB or SXB during inclusion except for the intervention dose. 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 * Coagulopathy or thrombocytopenia (\<100) * (Use of acetylsalicylic acid, NSAIDs, COX2 inhibitors or prophylactic low-molecular-weight heparin are no contraindications for lumbar puncture.) * Participants deemed at risk for brain replacement due to known aqueduct stenosis, Arnold chiari malformations. * Participants with a lumbo-sacral neural tube defect or who have a ventriculo-atrial or ventriculo-peritoneal drain. Contraindications for nVNS: * An active implantable medical device such as a pacemaker, deep brain stimulator, or any implanted electronic device. * A recent (\< 1 month) brain infarction or transient ischemic attack due to a symptomatic stenosis or dissection of the carotid artery (in these patients the other side will be stimulated unless a significant stenosis or dissection on the other side is present as well). * If someone knows to have a structural abnormality e.g. lymphadenopathy, previous surgery or abnormal anatomy (in these patients the other side will be stimulated) * Metal cervical spine hardware or metallic implant near the stimulation site * Cervical vagotomy (in these patients the other side will be stimulated) Contraindications for 7 Tesla MRI as determined by the 7 Tesla 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 Specific contraindications for checkerboard functional Magnetic Resonance Imaging (fMRI): * Seizure within prior year * Photosensitive epilepsy * Non-correctable visual impairment

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

Only the study team decides who joins. These are the ways to reach them.

  1. The places running it

    1 site. The list below names each one and where it is.

  2. The official record

    The full official record for this study. This one lists no contact details, but it is the first place any would appear.

    Open the record ↗

  3. A doctor treating you

    A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

  • Leiden University Medical Center (LUMC)

    Leiden, 2333ZA, Netherlands

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