PNS Therapy vs. Steroid Injections for Chronic Knee Pain

Overseen By Saba Javed, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Opioids

Disqualifiers: Cognitive dysfunction, Drug abuse, Infections, Allergies, others

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well different treatments improve movement in people with long-term knee pain. It compares standard steroid injections, a combination of peripheral nerve stimulation (a therapy using electrical impulses to ease pain) with steroid injections, and this stimulation with a placebo injection. Individuals experiencing persistent knee pain and difficulty moving their knees might be suitable candidates. Participants will receive a combination of these treatments to determine which is most effective for easing knee pain. As an unphased trial, this study provides participants the opportunity to explore innovative treatment combinations that could significantly enhance their quality of life.

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

The trial information does not specify if you need to stop taking your current medications. However, if you are on opioids for reasons other than knee pain, you cannot participate in the trial.

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

Studies have shown that peripheral nerve stimulation (PNS) is generally well-tolerated for chronic knee pain, with most patients experiencing significant pain relief. Possible side effects include infection, movement of the device, and skin problems.

Research has indicated that steroid injections, particularly those with triamcinolone and bupivacaine, are safe and effective for knee pain. Many studies report significant improvements in pain and stiffness over time. These injections are commonly used, well-understood, and have a good safety record.

Both treatments have shown positive results, but risks remain, as with most medical procedures. Prospective trial participants should discuss these risks with the research team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PNS (Peripheral Nerve Stimulation) therapy for chronic knee pain because it offers a novel approach to pain management. Unlike traditional treatments like steroid injections that primarily focus on reducing inflammation, PNS therapy works by directly stimulating nerves to interrupt pain signals. This method could provide longer-lasting relief with fewer side effects. Additionally, combining PNS with steroid injections, as explored in some trial arms, might enhance the overall effectiveness, offering a comprehensive strategy for managing chronic knee pain.

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

This trial will compare Peripheral Nerve Stimulation (PNS) therapy with steroid injections for chronic knee pain. Research has shown that PNS, which participants in this trial may receive, can effectively reduce chronic knee pain. In one study, 94.4% of patients who received PNS reported their pain was cut by at least half. Another study found that PNS reduced pain by an average of 64% while resting and 50% during activity.

Triamcinolone, a type of steroid, is another treatment option in this trial. It effectively relieves knee pain and can control pain when injected directly into the knee joint. Extended-release versions of triamcinolone offer longer-lasting relief for those who haven't found other treatments helpful. Both PNS and triamcinolone have strong evidence supporting their use for knee pain. ^{1 2 6 7 8}

Who Is on the Research Team?

Saba Javed, M D

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with chronic knee pain, treated at the MD Anderson Cancer Center. Eligible participants must have a baseline pain score of 4 or higher and be able to consent. Those with opioid use unrelated to knee pain, cognitive issues, skin infections, recent substance abuse history, or allergies to local anesthetics or steroids cannot join.

Inclusion Criteria

Patient signed informed consent

I have chronic knee pain with a pain score of 4 or higher, treated at MD Anderson.

Exclusion Criteria

Patients with recent history (<6 months) of drug or alcohol abuse

I am unable to make medical decisions due to cognitive issues.

I have an open skin wound or am on antibiotics for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a standard steroid injection, PNS therapy plus a standard steroid injection, or PNS therapy plus a placebo injection

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for changes in knee range of motion and pain scores at 30, 60, and 90 days from baseline

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Peripheral Nerve Stimulation
• Placebo
• Triamcinolone

Trial Overview The study compares three treatments: a standard steroid injection into the knee; peripheral nerve stimulation (PNS) plus steroid injection; and PNS with a placebo. The goal is to see which method best improves knee movement in patients suffering from chronic knee pain.

How Is the Trial Designed?

Group I: Group 3 (PNS therapy plus 1 placebo injection) Experimental Treatment 2 Interventions

Participants will receive PNS therapy plus 1 placebo injection.

Group II: Group 2 (PNS therapy plus 1 standard steroid injection). Experimental Treatment 3 Interventions

Participants will receive PNS therapy plus 1 standard steroid injection.

Group III: Group 1 (standard steroid injection) Experimental Treatment 2 Interventions

Participants will receive 1 standard steroid injection.

Bupivacaine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in European Union as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in Canada as Sensorcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

In a 26-week study involving 215 patients with osteoarthritis, hylan G-F 20 (HG-F 20) provided significantly better pain relief and functional improvement compared to triamcinolone hexacetonide (TH) at both 12 and 26 weeks.

HG-F 20 demonstrated a longer duration of effect and was better tolerated, with no patients discontinuing treatment due to lack of efficacy, while 15 patients treated with TH did discontinue for this reason.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, single-blind comparison of the efficacy and tolerability of hylan G-F 20 and triamcinolone hexacetonide in patients with osteoarthritis of the knee. Caborn, D., Rush, J., Lanzer, W., et al.[2015]

Dexamethasone sodium phosphate is as effective as triamcinolone acetonide in treating mild to moderate carpal tunnel syndrome (CTS), showing significant improvements in symptoms and nerve conduction parameters over four months.

Dexamethasone is a safer option since it does not carry the risk of permanent nerve injury associated with triamcinolone if accidentally injected into the nerve, and it also resulted in less post-procedural pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Ultrasound-Guided Particulate Versus Nonparticulate Steroid Injection in Carpal Tunnel Syndrome: An Open-Label Randomized Control Trial. Mathew, MM., Gaur, R., Gonnade, N., et al.[2022]

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]

In a study of 30 patients with severe knee osteoarthritis, the combination of intra-articular Botulinum toxin-A (BoNT-A) and Triamcinolone provided significantly better pain relief compared to Triamcinolone alone, particularly noted from 4 weeks to 6 months post-treatment.

The results indicate that using BoNT-A alongside steroids not only improves pain relief but also enhances functional outcomes, suggesting it could be a more effective treatment option for managing severe knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Study of Botulinum Toxin: A with Triamcinolone Compared to Triamcinolone alone in the treatment of Osteoarthritis of Knee. Shukla, D., Sreedhar, SK., Rastogi, V.[2022]

In a study of 45 patients undergoing bilateral total knee arthroplasty, the addition of steroids to local infiltration analgesia significantly reduced pain levels and improved rehabilitation outcomes compared to LIA without steroids, particularly in the first week post-surgery.

Steroid-treated knees showed better range of motion and quicker recovery of active straight leg raises, with no increase in complications or adverse effects observed over a 1-year follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Steroid in Local Infiltration Analgesia in One-Stage Bilateral Total Knee Arthroplasty: A Paired-Randomized Controlled Study. Chan, VWK., Chan, PK., Yan, CH., et al.[2022]

In a study involving 63 total knee arthroplasty patients, liposomal bupivacaine (LB) provided better pain relief during activity on the first postoperative day compared to standard bupivacaine (SB), with lower pain scores (4.4 vs 5.9).

Patients receiving LB also required fewer opioids in the first two days after surgery (51.2 vs 66.1 on day 1 and 39.5 vs 54.8 on day 2), indicating a potential benefit in reducing opioid consumption post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal Bupivacaine Versus Standard Bupivacaine in the Adductor Canal for Total Knee Arthroplasty: A Randomized, Controlled Trial. Hubler, CP., Bevil, KM., Greiner, JJ., et al.[2021]

In a study of 60 patients who underwent total knee arthroplasty (TKA), those receiving perineural injection therapy (PIT) showed significantly better pain management and functional outcomes compared to those receiving standard postoperative care, as measured by the WOMAC and VAS scores.

PIT demonstrated high clinical efficacy with 93.5% of patients reporting excellent or good outcomes, while also being a cost-effective and safe treatment option with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Perineural Injections Combined with Standard Postoperative Total Knee Arthroplasty Protocols in the Management of Chronic Postsurgical Pain After Total Knee Arthroplasty. Güzel, İ., Gül, D., Akpancar, S., et al.[2021]

In a study of 56 patients with overuse sports injuries, the long-acting anesthetic bupivacaine provided better pain relief in the first six hours after local corticosteroid injections compared to the short-acting lidocaine.

Both anesthetic groups showed similar long-term outcomes, with about two-thirds of patients experiencing significant pain relief and half achieving full recovery to sports, suggesting that while bupivacaine offers initial advantages, both options are effective for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long- or short-acting anesthetic with corticosteroid in local injections of overuse injuries? A prospective, randomized, double-blind study. Kannus, P., Järvinen, M., Niittymäki, S.[2013]

Adding dexamethasone to bupivacaine for femoral nerve blocks significantly prolonged the duration of analgesia from 18.8 hours to 25.7 hours, enhancing pain management after total knee replacement surgery.

While total morphine consumption was similar between the two groups, patients receiving dexamethasone required less morphine in the first 6 hours post-surgery, indicating improved early pain control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone as adjuvant for femoral nerve block following knee arthroplasty: a randomized, controlled study. Sherif, AA., Elsersy, HE.[2018]

Intraarticular triamcinolone acetonide significantly reduced acute pain after arthroscopic knee surgery, with lower pain scores observed from 6 to 24 hours post-surgery compared to the saline control group.

Patients receiving triamcinolone required significantly less rescue analgesia, with none requesting additional pain relief compared to 53% in the saline group, highlighting its efficacy as a local pain management option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraarticular triamcinolone acetonide for pain control after arthroscopic knee surgery. Wang, JJ., Ho, ST., Lee, SC., et al.[2022]

Citations

1. nature.com nature.com/articles/s41598-023-42608-x

Peripheral nerve stimulation for the treatment of chronic ... Our results are promising and show a considerable reduction in chronic pain, an opioid usage and improved in quality of life.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12372923/

60-Day Peripheral Nerve Stimulation in Chronic Knee Pain Eighteen patients were identified who underwent PNS-therapy, and 94.4% (17/18) of the patients achieved ≥ 50% pain relief (responders) following ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10771261/

Peripheral Nerve Stimulation in Chronic Knee Pain The primary outcome of the case series was a perceived percentage reduction in chronic pain six months after PNS implantation. Clinically ...

4. orthopedicreviews.openmedicalpublishing.org orthopedicreviews.openmedicalpublishing.org/article/115599-peripheral-nerve-stimulation-after-total-knee-arthroplasty-and-non-operable-patella-fracture

Peripheral Nerve Stimulation After Total Knee Arthroplasty ... In the first study, the average pain between five patients decreased by 64% at rest and 50% during active moments.14 In the other study, average ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1094715925003782

ID# 1902188 Single-Center, Retrospective Chart Review of ... A total of 80% of patients experienced ≥50% pain relief, underscoring the efficacy of 60-day PNS as a promising avenue for substantial knee pain reduction.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11801347/

Real-world long-term outcomes of peripheral nerve stimulation Patients report clinically meaningful long-term pain relief after receiving PNS through both 60-day and permanent implant systems.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1094715925000315

An Analysis of the MAUDE Data base and Implications for ... Our analysis of the MAUDE data base revealed that infection, lead migration, and skin erosion were the most commonly reported AEs associated with the use of ...

8. mdpi.com mdpi.com/2077-0383/14/11/3964

Patient-Reported Outcomes with Peripheral Nerve ... Results: PNS led to marked improvements in pain-related outcomes. The average pain intensity scores dropped from 8.5 at baseline to 4.25 at one year, and pain ...