Injectable Cold Energy Therapy for Knee Arthritis

(ICE Trial)

Not currently recruiting at 16 trial locations

Overseen By David Curd

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brixton Biosciences, Inc.

Must not be taking: Opioids, Anticoagulants

Disqualifiers: Rheumatoid arthritis, Raynaud's, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Neural Ice, an injectable cold therapy, can help manage knee pain from osteoarthritis. Researchers compare its effectiveness to a common corticosteroid injection, Triamcinolone acetate, to determine which provides better relief. Individuals with chronic knee osteoarthritis pain, despite trying treatments like pain relievers or physical therapy for at least three months, might be eligible to join. Participants will be observed for six months after receiving the treatment. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could lead to new pain management options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not have had certain knee injections recently and should not be on high doses of opioids. It's best to discuss your specific medications with the study investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Neural Ice therapy, which uses cold to manage pain, is generally well-tolerated in studies for knee osteoarthritis. Participants reported few side effects, and the treatment appeared safe for most individuals. Triamcinolone acetate, a corticosteroid used to reduce joint swelling, is FDA-approved for other uses, indicating its well-established safety. In past studies, it was also well-tolerated with few side effects. Overall, previous research suggests both treatments are safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Neural Ice injections for knee arthritis because they introduce a novel approach by using cold energy directly on specific nerves around the knee. Unlike typical treatments like corticosteroids, which work by reducing inflammation within the joint, Neural Ice targets the nerves that send pain signals, potentially offering pain relief without affecting the entire joint. This targeted delivery means it could minimize side effects associated with broader treatments, providing a more focused and potentially safer pain management option.

What evidence suggests that this trial's treatments could be effective for knee arthritis?

Research shows that Neural Ice, a treatment in this trial, is administered by injection and targets the nerves around the knee to reduce osteoarthritis pain. This treatment employs cryoneurolysis, which involves freezing the nerves to offer long-lasting pain relief. Previous studies with similar freezing techniques have shown that this approach can effectively reduce chronic pain. Although limited data exists specifically for Neural Ice, the method has shown promise in providing relief for similar conditions. Overall, the goal is to reduce pain and improve movement for people with knee arthritis. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults aged 22-80 with chronic pain from knee osteoarthritis can join this trial. Specific details on who can or cannot participate are not provided, so interested individuals should contact the study organizers for full eligibility criteria.

Inclusion Criteria

I've tried pain relief methods like NSAIDs, physical therapy, or injections for over 3 months without success.

I have long-term knee pain from arthritis, confirmed by an X-ray in the last year.

Willing/able to understand the informed consent form and provide written informed consent

Exclusion Criteria

History of cold urticaria

I've had surgery on my limb that may have affected its nerves or blood vessels.

Known allergy to glycerol, hyaluronic acid, poloxamer 407, or phosphate buffered saline

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Neural Ice or corticosteroid injections for knee osteoarthritis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Neural Ice
• Triamcinolone acetate

Trial Overview The trial is testing Neural Ice, a new treatment for managing chronic knee pain due to osteoarthritis, against Triamcinolone acetate, an established therapy. Participants will be monitored over six months and must keep diaries of their condition.

How Is the Trial Designed?

Group I: Neural Ice injections Experimental Treatment 1 Intervention

This therapy will be injected around the superolateral, superomedial, and inferomedial genicular nerves.

Group II: Corticosteroid injection Active Control 1 Intervention

Intraarticular corticosteroid injection is defined as a single dose of Triamcinolone 40mg injected directly into the joint space.

Neural Ice is already approved in United States for the following indications:

Approved in United States as Neural Ice therapy for:

• Chronic pain associated with osteoarthritis of the knee

Who Is Running the Clinical Trial?

Brixton Biosciences, Inc.

Lead Sponsor

Trials

1

Recruited

260+

Published Research Related to This Trial

Intra-articular injections of triamcinalone acetonide, a common glucocorticoid, can lead to cutaneous hypopigmentation, which is a rare but notable side effect.

This case highlights a unique pattern of hypopigmentation with a linear ray distribution, suggesting that the glucocorticoid may spread through lymphatic channels after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear rays of hypopigmentation following intra-articular corticosteroid injection for post-traumatic degenerative joint disease. Schwartz, C., Javvaji, S., Feinberg, JS.[2013]

Corticosteroid injections, commonly used for treating inflammatory rheumatic conditions, can lead to significant side effects, including a secondary Cushingoid state, even when administered locally and sporadically.

In four reported cases, patients developed symptoms such as moon face, buffalo hump, and menstrual cycle disturbances after receiving triamcinolone acetonide injections, highlighting the need for increased awareness among healthcare providers about these potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four cases of a secondary Cushingoid state following local triamcinolone acetonide (Kenacort) injection. Jansen, TL., Van Roon, EN.[2013]

A single intra-articular injection of triamcinolone acetonide extended-release (TA-ER) showed prolonged presence in the joint compared to the standard crystalline suspension, indicating its potential for sustained therapeutic effects in knee osteoarthritis.

The study found that while TA-ER and the crystalline form had similar mild effects on cartilage, the transient nature of these effects suggests that TA-ER's benefits may be more pronounced in diseased joints rather than in healthy ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs. Bodick, N., Williamson, T., Strand, V., et al.[2020]

Intralesional Kenalog (triamcinolone) is an effective treatment for skin conditions like nodulocystic acne, demonstrating its therapeutic potential.

However, this case highlights a rare but significant side effect: a granulomatous reaction, indicating that while the treatment is beneficial, it can also lead to adverse histopathological responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulomatous Reaction to Intralesional Kenalog (Triamcinolone) Injection in Acne: A Case Report. Song, Y., Guo, Y.[2020]

In a study of 60 children under 10 with pauci-articular juvenile chronic arthritis, 77% of treated knees showed excellent or good outcomes one year after receiving local injections of triamcinolone hexacetonide.

The treatment was effective in controlling disease activity, with only minor complications reported, such as small areas of subcutaneous tissue atrophy in 2 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triamcinolone into the knee joint in juvenile chronic arthritis. Earley, A., Cuttica, RJ., McCullough, C., et al.[2017]

In a study of 40 children with chronic arthritis, intraarticular injections of triamcinolone hexacetonide led to a 63.3% rate of complete resolution of knee inflammation at 6 months.

At 12 months, 45% of the treated knees remained in remission, with better outcomes associated with younger age, shorter disease duration, and higher doses of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarticular triamcinolone hexacetonide in the management of chronic arthritis in children. Allen, RC., Gross, KR., Laxer, RM., et al.[2019]

Intra-articular administration of triamcinolone hexacetonide (THG) significantly improved weight distribution and pain scores in patients over a period of 180 days compared to saline, with notable improvements starting as early as 8 days post-treatment.

The study involved 40 hip joints in children with a mean age of 6.5 years, and THG showed better outcomes in joint function and thermographic evaluations, indicating its efficacy in managing joint issues, although factors like age and radiographic findings influenced treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The intra-articular administration of triamcinolone hexacetonide in the treatment of osteoarthritis. Its effects in a naturally occurring canine osteoarthritis model. Alves, JC., Santos, A., Jorge, P., et al.[2023]

Triamcinolone acetonide extended-release (ER) 32 mg significantly reduces knee osteoarthritis pain over 24 weeks compared to placebo, while also improving stiffness and physical function, demonstrating its efficacy as a treatment option.

The formulation of triamcinolone acetonide ER in PLGA microspheres allows for prolonged release in the joint, minimizing systemic exposure and related side effects, making it a safer alternative to traditional corticosteroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. Paik, J., Duggan, ST., Keam, SJ.[2023]

The use of CryoVIVE® cryoanesthesia significantly reduced pain during intralesional triamcinolone injections for nodulocystic acne, with mean pain scores dropping from 5.933 without anesthesia to 3.667 with it (p = 0.0001).

The procedure was found to be safe, with no reported side effects, discoloration, or scarring, indicating that CryoVIVE® is a practical option for enhancing patient comfort during dermatologic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cold anesthesia for pain reduction during intralesional steroid injection for nodulocystic acne. Park, SJ., Shin, SH., Koh, YG., et al.[2023]

Using a cryotip to provide fast-acting cryoanesthesia significantly reduced pain during intralesional steroid injections for hypertrophic scars and keloids, with pain scores dropping from 7.87 to 2.7 on the visual analogue scale (VAS).

The study involved 30 patients and demonstrated that applying the cryotip before steroid injection not only alleviated pain effectively but could also enhance the overall therapeutic outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical cryoanesthesia for the relief of pain caused by steroid injections used to treat hypertrophic scars and keloids. Wang, X., Wu, X., Liu, K., et al.[2021]

In a double-blind study involving 30 patients with rheumatoid arthritis, all three intra-articular steroid preparations (prednisolone t-butyl acetate, methyl prednisolone acetate, and triamcinolone hexacetonide) showed thermographic improvement in knee synovitis, with triamcinolone demonstrating the greatest and longest-lasting effect.

Despite the local improvements in knee symptoms, no significant overall systemic improvement was observed after a single injection of any steroid, although all three preparations suppressed the body's natural cortisol production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A thermographic and clinical comparison of three intra-articular steroid preparations in rheumatoid arthritis. Bird, HA., Ring, EF., Bacon, PA.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06700109?intr=neural%20ice&rank=1

injectable cold energy therapy for the management of ... The goal of this clinical trial is to evaluate the effectiveness of Neural Ice for pain management associated with knee osteoarthritis in adults aged 22-80 ...

2. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06700109/injectable-cold-energy-therapy-for-the-management-of-chronic-pain-associated-with-osteoarthritis-of-the-knee

INJECTABLE COLD ENERGY THERAPY FOR THE ... The goal of this clinical trial is to evaluate the effectiveness of Neural Ice for pain management associated with knee osteoarthritis in adults

3. reporter.nih.gov reporter.nih.gov/project-details/11006862

Neural Ice Technology for Treatment of Pain Current cryoneurolysis methods apply very low-temperature cryoprobes to freeze peripheral nerves, resulting in reversible and long-lasting pain relief. However, ...

4. brixtonbio.com brixtonbio.com/nice-trial

NICE Trial NICE (Neural Injectable Cold Energy) Trial. Neural Injectable Cold Energy therapy for the management of chronic pain associated with osteoarthritis of the knee.

5. withpower.com withpower.com/trial/phase-osteoarthritis-10-2024-f7433

Injectable Cold Energy Therapy for Knee Arthritis (ICE Trial) The goal of this clinical trial is to evaluate the effectiveness of Neural Ice for pain management associated with knee osteoarthritis in adults aged 22-80 ...

6. vpr.uthscsa.edu vpr.uthscsa.edu/findastudy_amf/protocol/50110

Injectable Cold Energy Therapy for Osteoarthritis Knee Pain Evaluate the safety and analgesic performance of the Neural Ice™ device in subjects with moderate to severe pain due to osteoarthritis of the knee compared ...