Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06585384
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-31
Brief Title:
Safety of a Strategy Combining Etanercept Administration with Repeated Contrast Ultrasound in Patients with Alzheimers Disease
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Safety of a Strategy Combining Etanercept Administration with Repeated Contrast Ultrasound in Patients with Alzheimers Disease Phase I Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
BRAINWAVES
Brief Summary:
Alzheimers 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 Alzheimers 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
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 Alzheimers 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None