Alzheimer DiseasePhase 1BRAINWAVESNCT06585384
Safety of a Strategy Combining Etanercept Administration With Repeated Contrast Ultrasound in Patients With Alzheimer's Disease
A Phase 1 study testing etanercept and repeated contrast ultrasound in people with Alzheimer Disease, run by Fondation Ophtalmologique Adolphe de Rothschild at 1 site in France.
Trial summary
Alzheimer's disease (AD) is a clinico-pathological entity combining multiple and varied neuropathological lesions with characteristic abnormal accumulations (amyloid Beta (Aβ) plaques and neurofibrillary degeneration (NFD)), neuroinflammation, as well as neuronal and synaptic suffering. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- etanercept and repeated contrast ultrasound
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- 15 Apr 2025to Dec 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Positive diagnosis of Alzheimer's disease according to IWG2 criteria
- Biological profile in favour of Alzheimer's disease
- Age ≥ 50 years and ≤ 85 years
- Affiliated or beneficiary of a social insurance scheme
- Patient suffering from mild AD with little or no impact on autonomy, MMSE score ≥20 at inclusion
- Fazekas score <=1
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- Presence of a family or a person at home who can monitor the occurrence of adverse events
- Sufficient command of the French language to take neuropsychological tests.
- Have undergone a full neuropsychological assessment within 6 months.
- If anticholinesterase treatment, stability of treatment for at least three months.
- Signed, free and informed consent from the patient and the trusted support person.
Who cannot join
- Patient previously treated with anti-TNF alpha (e.g. etanercept).
- Other cause of major neurocognitive disorder.
- Participation in another drug study
- Absolute contraindication to MRI (e.g. pacemaker, implantable stimulator, intra-orbital metallic foreign body);
- Contraindication to lumbar puncture.
- History of bleeding diathesis;
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- Severe chronic respiratory disease;
- Patient on anticoagulant therapy
- Right-to-left shunt, severe pulmonary arterial hypertension;
- Known cerebral vasculopathy; (Fazekas greater than 1), sequelae of ACI.
- Treatment with Anakinra, abatacept or sulfasalazine.
- Patients who have undergone major surgery within 28 days of the first day of the study.
- Allergy to gadolinium, or any contraindication to contrast products used for brain imaging (in particular severe renal insufficiency with a glomerular filtration rate <30 ml / min / 1.73 m2).
- Allergy to xylocaine
- Epilepsy or drugs that lower the epileptogenic threshold (see Appendix 6).
- Major depressive syndrome despite appropriate treatment and/or psychotic symptoms (according to DSM IV);
- MRI characteristic of an active or acute neurological process (infection, tumour) or macro-haemorrhage.
- Non-menopausal women
- Patient benefiting from a legal protection measure other than guardianship or curatorship.
- Optic neuritis
- Manifestations of multiple sclerosis
- Live vaccinations (yellow fever, BCG) within 4 weeks of starting etanercept treatment.
- History of hepatitis B or C
- Patients with recent acute coronary syndrome or unstable ischaemic heart disease.
- History of recurrent or chronic infections, or a predisposing condition such as severe or poorly controlled diabetes.
- Patients who have undergone major surgery within 28 days of the first day of the study.
- Contraindications related to etanercept :
- Hypersensitivity to etanercept or to any of the excipients of Benepali
- Sepsis or risk of sepsis
- Active infection including chronic or localised infections.
- Contraindications associated with SonoVue (ultrasound contrast medium)
- Hypersensitivity to Sonovue.
- Right-to-left shunt
- Severe PAH (pulmonary arterial pressure greater than 90 mmHg)
- Uncontrolled hypertension
- Respiratory distress syndrome
- Conditions suggesting cardiovascular instability for which dobutamine is contraindicated
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jean Claude SADIK, PHD contact
France1 site, 1 recruiting
- Recruiting
Fondation Adolphe de Rothschld
Paris, 75019
Anne Caroline PAPEIX, MD-PHD, :+33148036617, cpapeix@for.paris
About this study
Official title: Safety of a Strategy Combining Etanercept Administration With Repeated Contrast Ultrasound in Patients With Alzheimer's Disease: Phase I Study
Alzheimer's disease (AD) is a clinico-pathological entity combining multiple and varied neuropathological lesions with characteristic abnormal accumulations (amyloid Beta (Aβ) plaques and neurofibrillary degeneration (NFD)), neuroinflammation, as well as neuronal and synaptic suffering.
To date, only symptomatic treatments are available, with no proven effect on neuropathological lesions or on the clinical course of the disease.
Read more
Anti-TNF alpha could be a therapeutic agent of choice in the treatment of central nervous sytem (CNS) diseases with an inflammatory component, such as AD. Unfortunately, their high molecular weight prevents them from passively crossing the blood brain barrier (BBB). In a pilot study published in 2006, etanercept was administered intrathecally to AD patients with encouraging clinical effects.
Transient opening of the tight junctions between the endothelial cells of the BBB by delivering High Intensity Focalised Ultrasounds (HIFU) in combination with an intravenous injection of microbubbles is a strategy that could improve bioavailability. Studies suggest that the oscillation of microbubbles in the ultrasound field generates microcurrents that induce shear forces responsible for a transient opening of the BBB. Ultrasound can be focused or unfocused and open the BBB diffusely or selectively over defined regions of the brain. This technique was first used to open the BBB in humans in 2001.
Transient opening of the BBB is also thought to modulate the immune response in the CNS, leading to a reduction in the intracerebral load of Aβ. In an Alzheimer's mouse model, several studies using ultrasound devices to open the BBB have shown a reduction in the intracerebral load of Aβ (up to 75%) and an improvement in the memory faculties and cognitive performance of the animals.
In humans, two clinical trials have assessed the safety of using ultrasound-assisted BBB disruption devices in AD patients. These were the Sonocloud® (Carthera) and ExAblate® (InSightec) devices. The Sonocloud® device is an extra-dural ultrasound emitter implanted under local anaesthetic. Enrolment was completed in October 2020, but the results of the trial are not yet available (NCT03119961). The phase I study on 5 patients evaluating the ExAblate® device coupled with the injection of gas microbubbles demonstrated reversible opening of the BBB with no serious adverse effects for the patients. No effect on intracerebral Aβ load or cognitive or behavioural improvement was demonstrated. The ExAblate® device is not implantable and is therefore less invasive than the Sonocloud® device. However, it requires MRI monitoring and the transducers used often generate high levels of heat, requiring the use of a water cooling system to avoid the risk of transducer deterioration.
In this project, our aim is to assess the safety of using a non-focused ultrasound device, the General Electric VIVID S70 clinical device (CE mark G1 023782 0112 ), to perform BBB ruptures in patients suffering from AD, combined with the administration of etanercept, whose bioavailability would thus be improved.
- Conditions
- Alzheimer Disease
- Being tested
- etanercept and repeated contrast ultrasound
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanercept and repeated contrast ultrasoundCombination product
Strategy combining 9 weeks of etanercept administration (50mg/week) with 5 weeks of repeated contrast ultrasound of 2 sessions per day, 5 days per week (from the fifth week of etanercept treatment)
| Study group | Role | What they receive |
|---|---|---|
| etanercept and repeated contrast ultrasound | Experimental | Not described Receives: Combination Product: etanercept and repeated contrast ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of a strategy combining 9 weeks of etanercept administration with 5 weeks of repeated contrast ultrasound of 2 sessions per day, 5 days per week (from the fifth week of etanercept treatment) in patients with Alzheimer's disease.
Number of patients presenting related adverse events (CTCAE v4.0)
Measured: from Day1 of repeated contrast ultrasound to Month 3 after the end of repeated contrast ultrasound
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2024
- Study start15 Apr 2025
- Primary completionJun 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- More trials run by Fondation Ophtalmologique Adolphe de RothschildThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondation Ophtalmologique Adolphe de Rothschild
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06585384
- Sponsor's protocol ID
- CPX_2023_4
- Acronym
- BRAINWAVES
- Status last verified
- May 2026
- First submitted
- 31 Jul 2024
- Last updated
- 12 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of a Strategy Combining Etanercept Administration With Repeated Contrast Ultrasound in Patients With Alzheimer's Disease: Phase I Study
- ClinicalTrials.gov ID
- NCT06585384
- Acronym / sponsor ID
- BRAINWAVES / CPX_2023_4
- Conditions
- Alzheimer Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- Fondation Ophtalmologique Adolphe de RothschildResearch network
- Study start
- 15 Apr 2025 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 5 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Alzheimer's disease (AD) is a clinico-pathological entity combining multiple and varied neuropathological lesions with characteristic abnormal accumulations (amyloid Beta (Aβ) plaques and neurofibrillary degeneration (NFD)), neuroinflammation, as well as neuronal and synaptic suffering.
To date, only symptomatic treatments are available, with no proven effect on neuropathological lesions or on the clinical course of the disease.
Anti-TNF alpha could be a therapeutic agent of choice in the treatment of central nervous sytem (CNS) diseases with an inflammatory component, such as AD. Unfortunately, their high molecular weight prevents them from passively crossing the blood brain barrier (BBB). In a pilot study published in 2006, etanercept was administered intrathecally to AD patients with encouraging clinical effects.
Transient opening of the tight junctions between the endothelial cells of the BBB by delivering High Intensity Focalised Ultrasounds (HIFU) in combination with an intravenous injection of microbubbles is a strategy that could improve bioavailability. Studies suggest that the oscillation of microbubbles in the ultrasound field generates microcurrents that induce shear forces responsible for a transient opening of the BBB. Ultrasound can be focused or unfocused and open the BBB diffusely or selectively over defined regions of the brain. This technique was first used to open the BBB in humans in 2001.
Transient opening of the BBB is also thought to modulate the immune response in the CNS, leading to a reduction in the intracerebral load of Aβ. In an Alzheimer's mouse model, several studies using ultrasound devices to open the BBB have shown a reduction in the intracerebral load of Aβ (up to 75%) and an improvement in the memory faculties and cognitive performance of the animals.
In humans, two clinical trials have assessed the safety of using ultrasound-assisted BBB disruption devices in AD patients. These were the Sonocloud® (Carthera) and ExAblate® (InSightec) devices. The Sonocloud® device is an extra-dural ultrasound emitter implanted under local anaesthetic. Enrolment was completed in October 2020, but the results of the trial are not yet available (NCT03119961). The phase I study on 5 patients evaluating the ExAblate® device coupled with the injection of gas microbubbles demonstrated reversible opening of the BBB with no serious adverse effects for the patients. No effect on intracerebral Aβ load or cognitive or behavioural improvement was demonstrated. The ExAblate® device is not implantable and is therefore less invasive than the Sonocloud® device. However, it requires MRI monitoring and the transducers used often generate high levels of heat, requiring the use of a water cooling system to avoid the risk of transducer deterioration.
In this project, our aim is to assess the safety of using a non-focused ultrasound device, the General Electric VIVID S70 clinical device (CE mark G1 023782 0112 ), to perform BBB ruptures in patients suffering from AD, combined with the administration of etanercept, whose bioavailability would thus be improved.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| etanercept and repeated contrast ultrasound | Experimental | Combination Product: etanercept and repeated contrast ultrasound |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Positive diagnosis of Alzheimer's disease according to IWG2 criteria
- Biological profile in favour of Alzheimer's disease
- Age ≥ 50 years and ≤ 85 years
- Affiliated or beneficiary of a social insurance scheme
- Patient suffering from mild AD with little or no impact on autonomy, MMSE score ≥20 at inclusion
Key exclusion criteria (37 listed)
- Patient previously treated with anti-TNF alpha (e.g. etanercept).
- Other cause of major neurocognitive disorder.
- Participation in another drug study
- Absolute contraindication to MRI (e.g. pacemaker, implantable stimulator, intra-orbital metallic foreign body);
- Contraindication to lumbar puncture.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| etanercept and repeated contrast ultrasoundStrategy combining 9 weeks of etanercept administration (50mg/week) with 5 weeks of repeated contrast ultrasound of 2 sessions per day, 5 days per week (from the fifth week of etanercept treatment) | Combination product | etanercept and repeated contrast ultrasound |
Primary outcome
To assess the safety of a strategy combining 9 weeks of etanercept administration with 5 weeks of repeated contrast ultrasound of 2 sessions per day, 5 days per week (from the fifth week of etanercept treatment) in patients with Alzheimer's disease.
Time frame: from Day1 of repeated contrast ultrasound to Month 3 after the end of repeated contrast ultrasound
Number of patients presenting related adverse events (CTCAE v4.0)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jean Claude SADIK, PHD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing etanercept and repeated contrast ultrasound in people with Alzheimer Disease, run by Fondation Ophtalmologique Adolphe de Rothschild at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Amélie Yavchitz (+33 1 48 03 64 54, ayavchitz@for.paris), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety of a strategy combining 9 weeks of etanercept administration with 5 weeks of repeated contrast ultrasound of 2 sessions per day, 5 days per week (from the fifth week of etanercept treatment) in patients with Alzheimer's disease. (time frame: from Day1 of repeated contrast ultrasound to Month 3 after the end of repeated contrast ultrasound). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.