Safety of a Strategy Combining Etanercept Administration With Repeated Contrast Ultrasound in Patients With Alzheimer's Disease

Eligibility criteria

Inclusion Criteria:
* 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
* 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.
Exclusion Criteria:
* 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;
* 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

The sponsor's own eligibility wording, lightly reformatted. The study team makes the final eligibility decision — worth discussing with your doctor.

Eligibility criteria as of 2026-05-12