Methylprednisolone for Knee Arthritis

Not yet recruiting at 1 trial location

Overseen By Johannes F Plate, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: F. Johannes Plate

Must not be taking: Chronic steroids, Opioids

Disqualifiers: Diabetes, Chronic pain, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the steroid methylprednisolone aids pain relief and movement after knee replacement surgery. The goal is to determine if taking this medication post-surgery improves recovery and patient satisfaction. Participants are divided into two groups: one receives the steroid during surgery, and the other receives it both during and after surgery. Individuals planning to undergo knee replacement surgery and capable of using a computer or smartphone to complete surveys may be suitable for this trial. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic steroid treatments or opioids for pain, you would not be eligible to participate.

What is the safety track record for methylprednisolone?

Research has shown that methylprednisolone is generally safe for humans. Studies on individuals with knee osteoarthritis found that injections of this medication relieve pain and improve physical movement. Participants in these studies did not report any major side effects, indicating the treatment is well-tolerated.

As this treatment is in a Phase 4 trial, it has already been tested on many people and is usually considered safe. Its approval for other uses further supports its safety. However, like any medication, some risks may still exist, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for knee arthritis because they incorporate methylprednisolone in a new way, potentially offering more effective relief. Unlike the standard of care, which often involves NSAIDs or corticosteroid injections, this approach combines intraoperative intravenous dexamethasone with a post-operative taper of methylprednisolone. This method aims to optimize anti-inflammatory effects right after surgery and sustain them during recovery, possibly leading to faster and more sustained pain relief. By targeting inflammation both immediately and over the following days, this treatment could enhance patient outcomes compared to existing therapies.

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

Previous studies have shown that methylprednisolone effectively reduces pain and improves physical function in patients with knee osteoarthritis. Research indicates that corticosteroid injections, such as methylprednisolone, provide significant symptom relief for up to 12 weeks. Patients reported better pain control and increased mobility after receiving these treatments. In this trial, one group will receive intraoperative intravenous dexamethasone only, while another group will receive both intraoperative dexamethasone and a 6-day post-operative methylprednisolone taper. The methylprednisolone taper aims to maintain pain relief following knee surgery, aiding recovery by managing pain and facilitating earlier joint movement. ^{1 2 3 4 6}

Who Is on the Research Team?

Johannes F Plate

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for individuals with knee arthritis who have undergone total knee arthroplasty. Participants should be interested in improving postoperative pain and range of motion. Specific inclusion and exclusion criteria are not provided, but typically would involve age, overall health status, and absence of conditions that could interfere with the study.

Inclusion Criteria

Access to computer or smartphone for completion of REDCap surveys

I am recommended to have a total knee replacement.

Exclusion Criteria

I am on long-term steroid medication.

Patients with allergies to steroids

Known diabetic patients with an HgbA1c >6.5 preoperatively

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intraoperative intravenous dexamethasone and a 6-day post-operative methylprednisolone taper

6 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including knee function, pain, and wound healing

3 months

2-week, 6-week, and 3-month postoperative visits

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone

Trial Overview The study tests if a tapering dose of methylprednisolone after surgery can improve functional outcomes compared to just using dexamethasone during surgery. A taper involves starting with a high dose then gradually reducing it over several days.

How Is the Trial Designed?

Group I: Intraoperative and Post-operative steroid Experimental Treatment 2 Interventions

Patients in this groups will receive intraoperative intravenous dexamethasone as well as a 6-day post-operative methylprednisolone taper

Group II: Intraoperative Steroid Active Control 1 Intervention

Patients randomized to this group will only receive intraoperative intravenous dexamethasone

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

Approved in United States as Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in European Union as Depo-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Approved in Canada as Solu-Medrol for:

• Allergic reactions
• Blood disorders
• Cancer
• Eye diseases
• Immune system disorders
• Inflammatory diseases
• Respiratory diseases
• Skin diseases

Who Is Running the Clinical Trial?

F. Johannes Plate

Lead Sponsor

Trials

1

Recruited

100+

Published Research Related to This Trial

In a study of 901 patients with relapsing-remitting multiple sclerosis, methylprednisolone (MP) pulse therapy was administered with a mean frequency of 4 times, showing that the majority of patients received treatment multiple times, indicating its common use in managing acute exacerbations.

The study found that female patients were approximately 3.7 times more likely to seek MP pulse therapy compared to male patients, suggesting a gender difference in treatment-seeking behavior for MS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary study related the incidence of methylprednisolone pulse therapy in patients visited multiple sclerosis clinic located at the isfahan kashani hospital. Tolou-Ghamari, Z., Shaygannejad, V., Ashtari, F.[2022]

Methylprednisolone acetate (Depo-Medrol) injections via epidural or intrathecal routes can effectively relieve diskogenic back pain and radiculopathy when conservative treatments have failed, particularly if symptoms have lasted less than three months.

Corticosteroid injections are less effective for patients with chronic symptoms lasting over three months or those who have previously undergone surgery, suggesting a limited window for optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of diskogenic pain using epidural and intrathecal steroids. Brown, FW.[2019]

Intramedullary injection of methylprednisolone acetate (Depo-Medrol) effectively treats unicameral cysts in children, as demonstrated in a rabbit model where the drug was injected into the tibia.

The study found that while serum levels of methylprednisolone rose quickly, indicating systemic absorption, there were no significant local histological changes such as fibroblastic proliferation or neovascularization, suggesting that the mechanism of action may not involve direct tissue alteration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The systemic and local effects of an intramedullary injection of methylprednisolone acetate in growing rabbits. Colville, MR., Aronson, DD., Prcevski, P., et al.[2019]

A case of conjunctival necrosis occurred in an 82-year-old patient after an inadvertent subconjunctival injection of methylprednisolone following cataract surgery, highlighting a serious complication associated with this medication.

Methylprednisolone is not approved for use in the eye, and this incident underscores the risks of using unapproved medications in ophthalmic procedures, emphasizing the need for caution and adherence to approved treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjunctival Necrosis due to Subconjunctival Methylprednisolone (Depo-Medrol™) Acetate Injection. van Zyl, LM., Hill, JJ.[2021]

The study found that the new high-dose (100 mg) methylprednisolone tablet has an absolute bioavailability of 82%, indicating it is effectively absorbed in the body when taken orally.

No adverse drug reactions were reported, and the tablet can safely substitute for intravenous methylprednisolone in high-dose therapy, as it produced expected changes in blood neutrophil counts without significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absolute bioavailability of a new high dose methylprednisolone tablet formulation. Groenewoud, G., Hundt, HK., Luus, HG., et al.[2013]

Inadvertent injection of methylprednisolone acetate into the eye during vitrectomy can lead to severe retinal toxicity, resulting in significant vision loss and complications such as retinal necrosis and optic nerve damage.

This case highlights the critical need for careful identification of medications during eye surgeries to prevent serious adverse effects associated with incorrect injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinal necrosis secondary to inadvertent intravitreal methylprednisolone acetate (depo-medrol) injection during pars plana vitrectomy. Yonekawa, Y., Sun, G., D'Amico, DJ., et al.[2014]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1743919118306265

Review Comparison of intra-articular hyaluronic acid and ... The present meta-analysis indicated that both HA and methylprednisolone were effective in reducing pain in knee OA and HA showed comparable effect to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5908555/

Intra-articular injection of methylprednisolone for reducing ... Intra-articular methylprednisolone injection was associated with an improved pain relief and physical function in patients with knee osteoarthritis.

3. journals.lww.com journals.lww.com/md-journal/fulltext/2018/04130/intra_articular_injection_of_methylprednisolone.8.aspx

Intra-articular injection of methylprednisolone for... : Medicine Intra-articular methylprednisolone injection was associated with an improved pain relief and physical function in patients with knee osteoarthritis.

4. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/acr2.11596

Corticosteroid Injections for Symptomatic Treatment of ... Corticosteroid injections demonstrated clinically meaningful improvements in KOA symptoms over 12 weeks of follow-up. These data support larger ...

5. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06163755

Comparison of Efficacy of Intra-articular Morphine vs ... Comparison of Efficacy of Intra-articular Morphine vs Methylprednisolone in Patients With Knee Osteoarthritis. A Single - Blind, Randomized-controlled Study.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10570668/

Corticosteroid Injections for Symptomatic Treatment ... Corticosteroid injections demonstrated clinically meaningful improvements in KOA symptoms over 12 weeks of follow‐up. These data support larger ...