Focused Ultrasound for Frailty

(fUS-ARF Trial)

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Neurological Associates of West Los Angeles

Disqualifiers: Pregnancy, Terminal illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment, transcranial ultrasound, for individuals with age-related frailty. The goal is to determine if this non-invasive brain treatment is safe and effective over time. The ultrasound targets the hypothalamus, a brain region involved in aging. Suitable candidates for this trial are those aged 60 to 95 who exhibit signs of frailty impacting daily life. As an Early Phase 1 trial, participants will be among the first to help researchers understand how this innovative treatment functions in people.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that transcranial ultrasound is safe for age-related frailty?

Research has shown that transcranial ultrasound is generally safe. This non-invasive technique checks blood flow in the brain without surgery or entering the body. Studies have found that patients tolerate it well, with no serious side effects reported in other uses.

Since this trial is in its early stages, it focuses on assessing safety and patient tolerance. Minor side effects might occur, but serious problems are not expected. As the treatment is still under study, more safety information will emerge as research continues.

Overall, existing evidence supports the safety of transcranial ultrasound, but new data from this trial will provide further insights. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial ultrasound for treating frailty because it offers a non-invasive approach that targets the hypothalamus directly. Unlike traditional treatments that might involve medication or physical therapy, this method uses focused ultrasound waves to potentially improve brain function and resilience. The precision of this technique, confirmed through MRI-guided targeting and advanced tracking technology, could lead to more effective interventions with fewer side effects. This innovative approach could revolutionize how we address frailty by enhancing the body's own regulatory systems without the need for drugs.

What evidence suggests that transcranial ultrasound is effective for age-related frailty?

Research has shown that transcranial ultrasound, the treatment under study in this trial, might improve brain function by boosting blood flow. Studies have found that low blood flow in the brain can slow movements and make physical tasks like walking or standing up more difficult. Transcranial ultrasound aims to increase this blood flow, potentially enhancing physical abilities in older adults. While more research is needed to confirm its effects on age-related frailty, this technique is promising because it targets brain areas involved in movement and energy. Early results suggest it could be a helpful treatment to explore further. ^{1 4 6 7 8}

Who Is on the Research Team?

Sheldon Jordan, MD

Principal Investigator

Neurological Associates - The Interventional Group

Are You a Good Fit for This Trial?

This study is for people aged 60-95 showing signs of frailty but not from another condition, scoring between 3 and 7 on the Frailty Scale. They must have a brain MRI with hypothalamus volume measured. It's not for those who can't lie still, are pregnant or breastfeeding, have terminal illness, can't consent, or have scalp issues.

Inclusion Criteria

Clinical appraisal by physician indicating signs of frailty (apart from a co-occuring condition), scoring 3<x<7 as denoted by the CSHA Clinical Frailty Scale (Rockwood, Song, MacKnight, et al, 2005; Golpanian, DiFede, Pujol, et al., 2016)

I have had an MRI of my brain that measured the size of my hypothalamus.

I am between 60 and 95 years old.

Exclusion Criteria

Pregnancy, women who may become pregnant or are breastfeeding

I have a scalp rash or open wounds on my scalp.

I am unable to understand and give consent for treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8 sessions of transcranial ultrasound treatment, each lasting 10 to 30 minutes

8 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Weekly follow-ups

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Ultrasound

Trial Overview The trial tests transcranial ultrasound as a treatment for age-related frailty. This Phase I open label study aims to assess its tolerability over time and potential effectiveness in improving symptoms of frailty.

How Is the Trial Designed?

Group I: Experimental Experimental Treatment 1 Intervention

Participants will undergo ten to thirty minutes of transcranial ultrasound treatment. The sanitation device will be aimed at the hypothalamus. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space.

Transcranial Ultrasound is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Doppler Ultrasonography for:

• Sickle Cell Disease
• Cerebral Ischemia
• Detection of Right-to-Left Shunts
• Subarachnoid Hemorrhage
• Brain Death
• Periprocedural or Surgical Monitoring

Approved in European Union as Transcranial Doppler Ultrasonography for:

• Sickle Cell Disease
• Cerebral Ischemia
• Detection of Right-to-Left Shunts
• Subarachnoid Hemorrhage
• Brain Death
• Periprocedural or Surgical Monitoring

Who Is Running the Clinical Trial?

Neurological Associates of West Los Angeles

Lead Sponsor

Trials

26

Recruited

4,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5729099/

Transcranial Doppler and lower extremity function in older adults Our data shows similar results - an association between low blood flow velocities in the MCA and worse gait speed and chair rise performance.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36400675/

Success Rate of Transcranial Doppler Scanning ... This study measured the rates of success in applying transcranial Doppler (TCD) scanning at the middle, posterior and anterior temporal windows (MTW, PTW and ...

3. ejns.springeropen.com ejns.springeropen.com/articles/10.1186/s41984-021-00114-0

Transcranial Doppler ultrasonography (uses, limitations, and ... Transcranial Doppler is a bedside procedure used to assess cerebral blood flow velocity via cerebral circulation and pulsatility index (PI).

4. researchgate.net researchgate.net/figure/Results-of-Transcranial-Doppler-Ultrasound-TCD-competency-evaluation-of-the-51-trainees_tbl1_338156850

Results of Transcranial Doppler Ultrasound (TCD) ... Almost half of the trainees (45%) successfully completed the competency evaluation-the pass rate for clinical scientists with ultrasound experience was 90% (9/ ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04583163

Variability in Transcranial Doppler Technique in Neuro- ... This study aims to determine the inter- and intra-variability of Transcranial Doppler (TCD) ultrasound in neuro-critical care patients who are planned for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3876587/

Transcranial Doppler Ultrasound: A Review of the Physical ... Transcranial Doppler (TCD) is a noninvasive ultrasound (US) study used to measure cerebral blood flow velocity (CBF-V) in the major intracranial arteries.

7. icm-experimental.springeropen.com icm-experimental.springeropen.com/articles/10.1186/s40635-025-00787-z

Transcranial ultrasound in the critically ill patient: a narrative ... Transcranial ultrasound is gaining widespread recognition as a useful bedside monitoring tool and non-invasive diagnostic device in the ...

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2022.841809/full

Transcranial Doppler Ultrasonography as a Diagnostic ... TCD provides data on venous hemodynamics that is not available from other neuroimaging modalities, and hence could be used to diagnose CSVT.