Triamcinolone Acetonide for Knee Osteoarthritis in Type 2 Diabetes

Overseen By Neil Segal, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Kansas Medical Center

Must be taking: Oral antidiabetics

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Rheumatoid arthritis, Active cancer, 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

Compensation: Varies

Number of Visits: 5

Duration: 1 day

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different treatments for knee osteoarthritis in people with type 2 diabetes, aiming to assess their effects on blood sugar levels. Participants will receive either a quick-release or an extended-release injection of triamcinolone acetonide, a corticosteroid. Individuals with type 2 diabetes managed without insulin and painful knee osteoarthritis may be ideal candidates for this study. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits more patients.

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

The trial does not specify if you need to stop your current medications, but it does require that your diabetes medication doses have been stable for at least one month before screening. Some medications, like certain corticosteroids, must not have been used recently, so it's best to discuss your specific medications with the trial team.

What is the safety track record for these treatments?

Research shows that both triamcinolone acetonide extended-release (TA-ER, known as Zilretta) and triamcinolone acetonide immediate-release (TA-IR, known as Kenalog) can affect blood sugar levels in people with type 2 diabetes. Studies involving patients with knee osteoarthritis and diabetes have found changes in blood sugar levels with these treatments. Therefore, individuals with diabetes should monitor their blood sugar closely when using these treatments.

Zilretta has FDA approval for treating knee pain from osteoarthritis, indicating thorough safety studies. It employs a special method to release the medication slowly over time. In contrast, Kenalog releases the medication all at once. Both are injected directly into the knee and are generally considered safe, but they can raise blood sugar levels. Patients, especially those with diabetes, should be aware of this and manage it properly. Always consult a healthcare professional if there are concerns or side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the treatments for knee osteoarthritis in individuals with type 2 diabetes because they offer innovative delivery methods for the active ingredient, triamcinolone acetonide. The extended-release form, ZILRETTA, uses PLGA microspheres to gradually release the medication over time, potentially providing longer-lasting relief compared to traditional options. On the other hand, Kenalog®-40 offers an immediate-release formulation, which could provide quicker relief. These formulations aim to improve the duration and onset of pain relief compared to standard corticosteroid injections, which typically offer only short-term benefits.

What evidence suggests that this trial's treatments could be effective for knee osteoarthritis in type 2 diabetes?

This trial will compare two forms of triamcinolone acetonide for knee osteoarthritis in individuals with type 2 diabetes. Studies have shown that the long-lasting form, triamcinolone acetonide extended-release (TA-ER), effectively treats knee osteoarthritis (OA) without significantly affecting blood sugar levels. Research indicates that TA-ER causes less disruption to blood sugar compared to the short-acting version, triamcinolone acetonide immediate-release (TA-IR). While the short-acting form is also used for knee OA, TA-ER may better manage blood sugar. For those with knee OA and diabetes, TA-ER might help avoid blood sugar spikes. Clinical evidence supports its effectiveness in relieving knee pain associated with OA. ^{6 7 8 9 10}

Who Is on the Research Team?

Neil A Segal, MD, MS

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

This trial is for people with Type 2 Diabetes (with HbA1C ≤9, not on insulin) and painful knee osteoarthritis. Participants should have a stable management plan for diabetes and meet specific clinical and radiological criteria to confirm their arthritis diagnosis.

Inclusion Criteria

I have had type 2 diabetes for at least one year.

I have been on stable diabetes medication for at least 1 month.

Written consent to participate in the study

Exclusion Criteria

My cancer is currently active.

I have had a joint injury, like a torn ACL, in the last year.

Previous or concomitant treatment-related criteria as specified

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 weeks

1 visit (in-person)

Pretreatment

Participants undergo a pretreatment phase with continuous glucose monitoring for baseline data collection

10 days

1 visit (in-person) for CGM sensor placement

Treatment

Participants receive intra-articular injection of either Zilretta or Kenalog

1 day

1 visit (in-person)

Post-treatment

Participants are monitored for blood glucose levels and other outcomes

12 weeks

2 visits (in-person) on Days 43 and 85, up to 4 phone visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• triamcinolone acetonide extended-release injectable suspension
• Triamcinolone Acetonide- Immediate Release

Trial Overview The study compares two treatments: Zilretta (an extended-release steroid injection) versus Kenalog (an immediate-release steroid injection), focusing on how they affect blood sugar levels in diabetic patients with knee osteoarthritis over approximately four months.

How Is the Trial Designed?

Group I: TA-IR Active Control 1 Intervention

Name: Kenalog®-40 (triamcinolone acetonide injectable suspension) Active Ingredient: Triamcinolone Acetonide- Immediate Release (TA-IR) Dosage: 40 mg/mL, IA, administered as a 1 mL Injection: TA-IR Mode of Administration: IA Knee Injection

Group II: TA-ER Active Control 1 Intervention

Name: ZILRETTA (triamcinolone acetonide extended-release injectable suspension; TA-ER) Active ingredient: Extended-release formulation of TA in 75:25 poly (lactic-co-glycolic) acid (PLGA) microspheres Dosage: Nominal 32 mg TA, intra-articular (IA) injection, administered as a 5 mL injection Mode of Administration: IA Knee Injection

triamcinolone acetonide extended-release injectable suspension is already approved in United States for the following indications:

Approved in United States as Zilretta for:

• Management of osteoarthritis pain of the knee

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Published Research Related to This Trial

The study found that combining local anesthetics (lidocaine, ropivacaine, and bupivacaine) with the novel triamcinolone acetonide extended-release (TA-ER) formulation does not negatively affect its physical or chemical properties, ensuring its efficacy remains intact.

This compatibility suggests that in clinical practice, local anesthetics can be safely added to TA-ER injections for knee osteoarthritis pain without compromising the treatment's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics. Jackson, JD., Cotton, L., Turkington, M., et al.[2020]

In a phase 3b study involving 208 patients with knee osteoarthritis, repeat injections of triamcinolone acetonide extended-release (TA-ER) were found to be safe and well tolerated, with no unexpected adverse events or significant changes in knee radiographs after 52 weeks.

Both the first and second injections of TA-ER provided similar and substantial pain relief, with most patients experiencing at least a 50% reduction in pain, indicating effective symptom management across varying severities of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Repeat Administration of Triamcinolone Acetonide Extended-release in Osteoarthritis of the Knee: A Phase 3b, Open-label Study. Spitzer, AI., Richmond, JC., Kraus, VB., et al.[2020]

In a study involving 30 children with non-infectious uveitis, subtenon triamcinolone acetonide (STA) injections showed significant efficacy, with 85.4% of eyes experiencing inflammation improvement and 77.8% resolution of macular edema at the 3-month follow-up.

The procedure was safe, with no immediate complications reported, and only a 12.5% incidence of ocular hypertension at 6 months, indicating that STA injections are a well-tolerated treatment option for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subtenon Triamcinolone Acetonide Injection with Topical Anesthesia in Pediatric Non-Infectious Uveitis. Jung, JL., Harasawa, M., Patnaik, JL., et al.[2023]

In a study of 33 patients with knee osteoarthritis and type 2 diabetes, the extended-release formulation of triamcinolone acetonide (TA-ER) resulted in significantly lower increases in blood glucose levels compared to the standard formulation (TAcs) after injection.

TA-ER also allowed for a greater percentage of time spent within the target blood glucose range (70-180 mg/dl) and reduced the time spent above 180 mg/dl, suggesting it may be a safer option for managing osteoarthritis pain in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. Russell, SJ., Sala, R., Conaghan, PG., et al.[2019]

Intra-articular injections of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TA) significantly raised blood glucose levels in patients with controlled diabetes and symptomatic osteoarthritis of the knee, with peak levels observed 24 to 32 hours post-injection.

In contrast, patients receiving hyaluronic acid (HA) injections did not experience significant increases in blood glucose, indicating that the rise in glucose levels is specifically associated with the steroid injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of intra-articular triamcinolone preparations on blood glucose levels in diabetic patients: a controlled study. Habib, GS., Miari, W.[2022]

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]

In a Phase-2 study involving 228 patients with knee osteoarthritis, the 40-mg dose of FX006, an extended-release formulation of triamcinolone acetonide, provided significantly better pain relief compared to immediate-release triamcinolone acetonide at multiple time points from five to twelve weeks.

The study found that FX006 was generally safe, with adverse events being mild and similar across all treatment groups, indicating that it is a promising option for managing knee osteoarthritis pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An intra-articular, extended-release formulation of triamcinolone acetonide prolongs and amplifies analgesic effect in patients with osteoarthritis of the knee: a randomized clinical trial. Bodick, N., Lufkin, J., Willwerth, C., et al.[2016]

In a study of 145 patients with severe bronchial asthma, repeated intramuscular injections of triamcinolone acetonide (Kenalog) resulted in excellent or good outcomes in 88.3% of cases, indicating its high efficacy for patients who did not respond to other treatments.

While Kenalog was effective, 13.8% of patients experienced side effects such as weight gain and increased blood pressure, highlighting the need for careful monitoring during prolonged steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of triamcinolone acetonide in the treatment of severe intrinsic bronchial asthma. Romański, B., Pawlik, K., Wilewska-Klubo, T.[2013]

Citations

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Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in ... The primary outcome will be measured 72 hours after treatment by a sensor automatically uploading the data, thus we expect few dropouts are expected. Official ...

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Triamcinolone Acetonide Extended-Release Effective for ... These data suggest that TA-ER may be an effective treatment for symptomatic knee OA without introducing blood glucose complications. Clinicians ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883540324005278

Extended-Release Versus Immediate ... Triamcinolone acetonide extended-release (TA-ER) was associated with minimal glycemic control disruption compared with triamcinolone acetonide immediate- ...

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Systemic Exposure & Diabetes Study | ZILRETTA® Safety Contraindication: ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids, or any components of the product.

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Safety and Systemic Exposure of Triamcinolone Acetonide ... Finally, results of a double-blind randomized study in patients with type 2 diabetes mellitus and knee OA showed changes in blood glucose levels, as detected ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/208845s000lbl.pdf

4163229 This label may not be the latest approved by FDA ... Corticosteroids may increase blood glucose concentrations. In a study where 18 patients with osteoarthritis knee pain and controlled type 2 diabetes mellitus ...

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About ZILRETTA® | How Microsphere Technology Works ZILRETTA is the first and only FDA-approved treatment for osteoarthritis knee pain that uses extended-release microsphere technology.

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Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in ... Subjects should have Type 2 Diabetes Mellitus (T2DM) with HbA1C ≤9 that is managed without insulin and have been diagnosed with symptomatic unilateral or ...