None listed
Conditions
Brief summary
The present study aim is to evaluate the safety, tolerability and feasibility of repeat SUSonly treatments in participants with AD using a bespoke low frequency transcranial SUS investigational device termed UltraTheraPilot.
Interventions
Neuromodulation using Scanning Ultrasound (SUSonly) is being investigated as a potential non-invasive therapy for Alzheimer’s disease (AD) as it has been shown to restore memory in senescent mice with memory impairment (Blackmore, Mol Psy, 2021). A mechanism has been identified that is relevant for AD pathology. The present study aim is to evaluate the safety, tolerability and feasibility of repeat SUSonly treatments in participants with AD using a bespoke low frequency transcranial SUS investig
Neuromodulation using Scanning Ultrasound (SUSonly) is being investigated as a potential non-invasive therapy for Alzheimer’s disease (AD) as it has been shown to restore memory in senescent mice with memory impairment (Blackmore, Mol Psy, 2021). A mechanism has been identified that is relevant for AD pathology. The present study aim is to evaluate the safety, tolerability and feasibility of repeat SUSonly treatments in participants with AD using a bespoke low frequency transcranial SUS investigational device termed UltraTheraPilot. The SUSonly intervention will be delivered across several face-to-face sessions with each individual participant. Therapy consists of four SUSonly treatments administered fortnightly for an overall duration of 6 weeks. The first 4 participants will be allocated to Cohort 1 targeting the precuneus (30 cubic centimetres of brain volume) and the following 8 participants will be allocated to Cohort 2 targeting the precuneus and flanking superior parietal lobe (100 cubic centimetres of brain volume). Participants in cohort 1 will receive 30 ultrasound pulses of 10 Hz administered to the region of interest, each pulse is approximately 6 s. Participants in cohort 2 will receive 100 ultrasound pulses of 10 Hz administered to the region of interest. The ultrasound parameters are the same for all participants, however, the sonication targets are individualised to target the region of interest using image guided navigation and the participant’s MRI data. Once inducted into the study, participants will undergo baseline assessments, including cognitive tests, EEG and MRI. Participant cognitive tests and EEGs will be conducted at the Queensland Brain Institute by qualified personnel, while MRI will be conducted at the Centre for Advanced Imaging. Participant screening and each SUSonly treatment session will be administered at the Mater Hospital Brisbane by the Principal Investigator. The principal investigator is a clinical neurologist who will monitor and document adherence to the intervention in the case report forms. The Principle Investigator has been trained by device technicians to use the UltraTheraPilot system to deliver SUSonly to the regions of interest. The safety of SUSonly will be determined by clinical assessment, MRI and behavioural tests. Participant tolerability of both the device and the SUSonly procedure will include MRI assessment.
Sponsors
The University of Queensland
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
All of the following inclusion criteria must be met for enrolment: 1. Biomarker confirmed AD: Clinical profile consistent with AD plus either (i) Positive amyloid scan (NAV4694 F18, florbetaben F18, florbetapir F18, or flutametamol F18) at or prior to screening, as read by the certified, site-designated PET scan reader or (ii) AD diagnosis by CSF biomarker analysis prior to screening. 2. MMSE equal or > 10 3. Age 50-85 4. Clinically stable in the investigator’s opinion 5. If on anti-dementia drugs or other psychoactive medications such as Aricept participants must be on stable doses of drug for at least 2 months 6. Participant’s legally designated representative must be able to freely give written informed consent; additionally, if, in the clinical judgment of the Principal Investigator, the participant themselves has the mental capacity to provide consent, they will also provide consent 7. Ability to comply with study regimen and provide contact phone number 8. Ability to communicate during procedures 9. Presence of a regular caregiver (in contact with participant daily) who can attend appointments and provide information about adverse events.
Exclusion criteria
None of the following exclusion criteria must be met for enrolment: 1. MRI contraindications: a. Metallic objects in head, or presence of unknown or MR unsafe devices anywhere in body or, b. Unable to tolerate MRI scanning (e.g. claustrophobia or known inability to lie sufficiently still from previous MRI scans) 2. Haemorrhages (including microhaemorrhages) on MRI scan (expected to be rare) 3. Any other MRI findings that in the opinion of the clinician may be contributing to the clinical profile, including severe ischemic changes, active or chronic infection/inflammation, tumour/space occupying lesion 4. Paget’s disease of bone 5. Clotting/bleeding disorder (including use of oral anticoagulants; anti-platelet therapy such as low-dose aspirin permitted) 6. Scalp or skull abnormalities a. Prior neurosurgical intervention of the brain / craniotomy or, b. Skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), open wounds, or atrophy of the scalp 7. Other neurological diseases (or history of): severe traumatic brain injury, seizure disorders, stroke, tumours, transient ischemic attack a. Cerebral pathology unrelated to Alzheimer’s disease 8. History of major psychiatric disorders (such as major depression or schizophrenia) 9. History of drug or alcohol abuse 10. An active inflammatory disease 11. Recent history (within four weeks prior to screening) of a clinically significant bacterial, fungal, or mycobacterial infection 12. Change of allowed, chronic, concomitant medication within 28 days prior to screening 13. Pregnancy or breast-feeding 14. Any other major medical illness that in the opinion of the clinician could interfere with the intended use (e.g. unstable cardiovascular, pulmonary, hepatic or renal disease, active cancer etc.) 15. Any conditions that render the participant unable to lie flat for scanning 16. Known cerebral or systemic vasculopathy 17. Corticosteroid treatment within last 6 weeks before first treatment 18. Increased intracranial pressure 19. Known skin allergies or sensitivity to silicone, ultrasound gel or depilation cream 20. Participation in other clinical trials within 90 days from the screening date 21. An inability to communicate during a treatment procedure 22. A body weight exceeding 200 kg 23. Other conditions implying increased risk according to the judgement of the investigator
Outcome results
None listed