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

Trial Summary

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 data supports the effectiveness of the drug triamcinolone acetonide extended-release for knee osteoarthritis in patients with type 2 diabetes?

Research shows that triamcinolone acetonide extended-release (TA-ER) significantly reduces knee pain and improves physical function in patients with osteoarthritis, with a similar safety profile to other treatments. It also has a prolonged effect due to its slow release in the joint, which helps manage pain without significantly raising blood sugar levels in patients with type 2 diabetes. ^{1 2 3 4 5}

Is triamcinolone acetonide safe for humans?

Triamcinolone acetonide, including its extended-release form (Zilretta), is generally well tolerated in humans for conditions like knee osteoarthritis, with a safety profile similar to placebo. However, it can cause side effects such as weight gain, increased blood pressure, and elevated blood glucose levels, especially in people with type 2 diabetes. ^{2 4 5 6 7}

How is the drug triamcinolone acetonide extended-release different from other treatments for knee osteoarthritis in type 2 diabetes?

Triamcinolone acetonide extended-release is unique because it uses microspheres to slowly release the medication in the knee joint, providing longer-lasting pain relief and reducing the risk of raising blood sugar levels, which is important for patients with type 2 diabetes. ^{1 3 4 5 8}

What is the purpose of this trial?

A Phase 2 Randomized Study to Evaluate the Effects of triamcinolone acetonide extended-release (TA-ER; Zilretta) vs. triamcinolone acetonide immediate-release (TA-IR; Kenalog) on Blood Glucose Levels in Diabetic Subjects with Knee Osteoarthritis. Subjects should have Type 2 Diabetes Mellitus (T2DM) with HbA1C ≤9 that is managed without insulin and have been diagnosed with symptomatic unilateral or bilateral osteoarthritis (OA) of the knee, based on clinical and radiological criteria (if bilateral, then a target knee will be selected).Total study duration for individual subject will be about 4 months, which includes 3 weeks of Screening period, 10 days of pretreatment phase, treatment day, and 12 weeks of post-treatment period.

Research Team

Neil A Segal, MD, MS

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

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

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

My cancer is currently active.

Previous or concomitant treatment-related criteria as specified

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics. [2020]

2. England 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. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Triamcinolone acetonide extended-release in patients with osteoarthritis and type 2 diabetes: a randomized, phase 2 study. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Triamcinolone Acetonide Extended-Release: A Review in Osteoarthritis Pain of the Knee. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Subtenon Triamcinolone Acetonide Injection with Topical Anesthesia in Pediatric Non-Infectious Uveitis. [2023]

7. Singapore pubmed.ncbi.nlm.nih.gov

The use of triamcinolone acetonide in the treatment of severe intrinsic bronchial asthma. [2013]

8. United States 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. [2016]