Ultrasound Stimulation for Arthritis

Overseen By Paul Pickrell, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Surf Therapeutics

Must be taking: Immunomodulatory medications

Must not be taking: JAK inhibitors, TNF inhibitors

Disqualifiers: Obesity, Pregnancy, Substance use, 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: 7

Duration: 5 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ultrasound treatment can reduce inflammation in individuals with types of arthritis such as Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis. Participants will undergo ultrasound sessions, with some receiving real Ultrasound Stimulation and others receiving a sham (fake) treatment for comparison. The trial focuses on tracking changes in inflammation markers in the blood. This study may suit individuals who have had one of these arthritis conditions for at least six months and are on a stable medication regimen. As an unphased trial, it offers a unique opportunity to contribute to innovative research that could lead to new treatment options for arthritis.

Will I have to stop taking my current medications?

Participants with Inflammatory Arthritis can continue their current stable dose of immunomodulatory medications while in the study. However, if you have recently started or changed certain medications like JAK inhibitors, DMARDs, or corticosteroids, you may not be eligible to participate.

What prior data suggests that this ultrasound stimulation is safe for people with inflammatory arthritis?

Research shows that ultrasound treatments are generally safe. A 2012 review examined various uses of therapeutic ultrasound and found it well-tolerated with few side effects. Another study discovered that focused low-intensity pulsed ultrasound effectively reduces pain and improves movement in people with knee osteoarthritis.

Furthermore, research from Sunnybrook Health Sciences Centre demonstrated that focused ultrasound is safe and effective for treating symptoms of certain conditions. This suggests that ultrasound therapy could be a useful tool for managing pain in muscle and bone issues. Overall, these studies support the safety of ultrasound treatments, although individual experiences may differ. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for arthritis that often rely on medications like NSAIDs or corticosteroids to reduce inflammation and pain, ultrasound stimulation offers a non-invasive and drug-free approach. This method uses sound waves to potentially reduce pain and improve joint function without the side effects associated with long-term medication use. Researchers are excited about ultrasound stimulation because it could provide a quicker and safer way to manage arthritis symptoms, making it an appealing option for those looking for alternative treatments.

What evidence suggests that ultrasound stimulation is effective for inflammatory arthritis?

Research has shown that ultrasound can help with arthritis by reducing pain and improving movement. In this trial, participants will receive either active ultrasound stimulation or non-active ultrasound stimulation (sham) during their visits. One study demonstrated that ultrasound treatment safely eased pain and improved mobility in people with knee arthritis. Another study found that low-intensity pulsed ultrasound improved blood flow and aided tissue healing. These studies suggest that ultrasound might effectively manage arthritis symptoms by reducing swelling and aiding tissue repair. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with various forms of inflammatory arthritis, such as rheumatoid arthritis and ankylosing spondylitis. Participants should be willing to undergo ultrasound stimulation sessions.

Inclusion Criteria

I am between 22 and 75 years old with inflammatory arthritis.

I weigh at least 40 kg.

I have been diagnosed with Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis for at least 6 months.

Exclusion Criteria

I do not have any health conditions that would prevent me from safely participating in a study.

Inflammatory Arthritis Population: History of substance use disorder or likely use of substances during the study period (marijuana, opioids/heroin, cocaine, psychedelics, methamphetamine, etc.)

I currently have an active bacterial or viral infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 ultrasound sessions, with 3 active and 2 sham treatments, to assess anti-inflammatory response

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for changes in pro-inflammatory cytokines at 2 hours and 24 hours post-therapy

1 week

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Non-active ultrasound stimulation
• Ultrasound Stimulation

Trial Overview The study tests if non-invasive ultrasound can reduce inflammation compared to a sham (placebo) intervention in people with inflammatory arthritis. Blood levels of inflammation markers are measured before and after the treatment.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Participants will receive active treatment during the visit. There will be a total of 5 visits involving ultrasound, with 2 being a sham and 3 being active. Patient is blinded to the treatment. The visit in which the sham is administered will be determined according to the Randomization Table

Group II: Control Placebo Group 1 Intervention

Participants will receive a non-active treatment during the visit. There will be a total of 5 visits involving ultrasound, with 2 being a sham and 3 being active. Patient is blinded to the treatment. The visit in which the sham is administered will be determined according to the Randomization Table

Ultrasound Stimulation is already approved in European Union for the following indications:

Approved in European Union as Focused Ultrasound Therapy for:

• Back pain secondary to facet joint arthritis

Who Is Running the Clinical Trial?

Surf Therapeutics

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

A systematic review of 35 randomized controlled trials found that therapeutic ultrasound has limited evidence of being more effective than placebo for treating pain and musculoskeletal injuries, with only 2 out of 10 methodologically sound studies showing some effectiveness for specific conditions like carpal tunnel syndrome and calcific tendinitis.

Overall, the majority of trials indicated that active therapeutic ultrasound does not significantly outperform placebo ultrasound, raising questions about its efficacy and the variability in treatment dosages used across studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of therapeutic ultrasound: effectiveness studies. Robertson, VJ., Baker, KG.[2022]

In a study of 33 patients with knee osteoarthritis, therapeutic ultrasound significantly improved pain relief and function as measured by the WOMAC scores, compared to a placebo group.

While both groups experienced reduced pain, ultrasound treatment did not lead to any changes in cartilage thickness, indicating it may help with symptoms but not with cartilage repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Therapeutic Ultrasound on Clinical Parameters and Ultrasonographic Cartilage Thickness in Knee Osteoarthritis: A Double-Blind Trial. Özgönenel, L., Okur, SÇ., Dogan, YP., et al.[2022]

In a study involving 40 healthy volunteers, focused ultrasound stimulation of the PC-6 acupuncture point significantly increased blood flow volume and skin temperature in the fingers and toes, indicating enhanced circulation.

Participants reported a warmer sensation in their toes after stimulation, as measured by a visual analog scale, suggesting that focused ultrasound may effectively alleviate coldness in extremities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound PC-6 Stimulation Effects on Blood Flow Volume, Skin Temperature, and Coldness of the Finger and Toe. Tsuruoka, N., Katayama, S., Seki, T., et al.[2020]

Therapeutic ultrasound significantly reduces knee pain in patients with osteoarthritis, with a strong effect size (SMD = -0.93) based on a systematic review of 10 randomized controlled trials involving 645 patients.

The treatment also improves physical function, as indicated by a reduction in the Western Ontario and McMaster Universities physical function score (SMD = -0.37), and no adverse events were reported, suggesting it is a safe intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapeutic ultrasound on pain, physical functions and safety outcomes in patients with knee osteoarthritis: a systematic review and meta-analysis. Zhang, C., Xie, Y., Luo, X., et al.[2018]

Pulsed focused ultrasound can effectively stimulate nerve structures and neurons, showing potential for various medical applications, including diagnosing neurological diseases and assessing skin and tissue sensitivity.

This technique may also aid in diagnosing hearing disorders and providing auditory information to individuals with specific types of hearing loss, highlighting its versatility in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of focused ultrasound for stimulation of nerve structures. Gavrilov, LR.[2019]

Daily application of low-intensity pulsed ultrasound stimulation (LIPUS) to intact tibias influences bone proteins related to mechanotransduction and growth factor signaling, specifically increasing focal adhesion kinase (FAK) and extracellular signal-regulated kinase-1/2 (ERK-1/2) expression at different time points during treatment.

LIPUS shows a noncumulative effect on these proteins, indicating that while it can modulate pathways involved in bone formation, the effects may diminish over time, particularly for insulin receptor substrate-1 (IRS-1).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity ultrasound increases FAK, ERK-1/2, and IRS-1 expression of intact rat bones in a noncumulative manner. de Gusmão, CV., Pauli, JR., Saad, MJ., et al.[2021]

A novel, wearable ultrasound platform showed a significant pain reduction of up to 52% in patients with knee osteoarthritis during two pilot studies.

Initial data suggests that ultrasound therapy may also improve mobility in patients with mild to moderate knee arthritis, indicating potential clinical benefits for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Clinical Studies of Long Duration, Low Intensity Therapeutic Ultrasound for Osteoarthritis. Langer, MD., Levine, V., Taggart, R., et al.[2020]

Therapeutic ultrasound is widely used for treating soft tissue injuries, which are common in rheumatic conditions, but there is limited evidence supporting its effectiveness in clinical settings.

The lack of clear benefits may stem from various factors, including technical differences in ultrasound application, the complexity of soft tissue injuries, and methodological issues in existing studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound in soft tissue lesions. Speed, CA.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31382781/

Effects of therapeutic ultrasound for knee osteoarthritis Therapeutic ultrasound is a safe treatment to relieve pain and improve physical function in patients with knee osteoarthritis.

2. fusfoundation.org fusfoundation.org/diseases-and-conditions/arthritis/

Arthritis A recent clinical trial was completed in Japan and revealed that MRgFUS ablation was both safe and effective at treating chronic pain caused by ...

3. nature.com nature.com/articles/srep35453

Efficacy of focused low-intensity pulsed ultrasound therapy ... FLIPUS is a safe and effective treatment modality for relieving pain and improving the functions and quality of life of patients with KOA.

4. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1292473/full

Effectiveness of low-intensity pulsed ultrasound on ... This modality is known to enhance local circulation and lymphatic circulation, improve metabolism, promote tissue regeneration and nutrient ...

5. cochrane.org cochrane.org/evidence/CD003132_therapeutic-ultrasound-osteoarthritis

Therapeutic ultrasound for osteoarthritis -People who used a fake therapeutic ultrasound had an improvement in their pain of about 2 on a scale from 0 to 10 after using it up to 2 months ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11796337/

Overview of Therapeutic Ultrasound Applications and Safety ... A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1063458414011984

The potential utility of high-intensity ultrasound to treat ... This review identifies high-intensity ultrasound (HIU) as a non-contact technique to modify articular cartilage and subchondral bone.

8. fusfoundation.org fusfoundation.org/the-technology/overview/

Overview Researchers at Sunnybrook Health Sciences Centre published data indicating that focused ultrasound is safe and effective in addressing the symptoms of ...

9. journals.sagepub.com journals.sagepub.com/doi/10.1177/20406223241267217

Ultrasound therapy for pain reduction in musculoskeletal ... This systematic review and meta-analysis aim to assess the effectiveness of ultrasound therapy in alleviating pain associated with musculoskeletal diseases.