Comparing Zilretta and Kenalog for knee osteoarthritis in patients with type 2 diabetes

RCT to Evaluate the Effects of Zilretta (Triamcinolone Acetonide- Extended Release) and Kenalog (Triamcinolone Acetonide- Immediate Release) on Blood Glucose in Subjects With Osteoarthritis of the Knee and Type 2 Diabetes Mellitus

This study is testing whether two different types of knee injections can help people with knee osteoarthritis and type 2 diabetes manage their symptoms while keeping their blood sugar levels stable.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (other)
• Locations: 1 site (Kansas City, Kansas)
• Trial ID: NCT06478186 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effects of two formulations of triamcinolone acetonide—extended-release (Zilretta) and immediate-release (Kenalog)—on blood glucose levels in patients with knee osteoarthritis and type 2 diabetes. Participants will be randomly assigned to receive either treatment through intra-articular injections. The study will last approximately four months, including screening, treatment, and post-treatment phases. The aim is to determine which formulation better manages osteoarthritis symptoms while maintaining stable blood glucose levels.

Who should consider this trial

Good fit: Ideal candidates are adults aged 40 and older with type 2 diabetes managed without insulin and symptomatic knee osteoarthritis.

Not a fit: Patients with uncontrolled diabetes, those requiring insulin, or with severe kidney issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for managing knee osteoarthritis in patients with type 2 diabetes.

How similar studies have performed: Other studies have explored similar corticosteroid treatments, but this specific comparison of extended vs. immediate release in diabetic patients is novel.

Eligibility criteria

Inclusion Criteria:

* 1\. Written consent to participate in the study. 2. Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions.

  3\. Male or female ≥40 years of age. 4. Females with negative pregnancy test, who are not breastfeeding and have no intention to become pregnant during the time from screening through EOS.

  5\. Type 2 DM for at least 1 year prior to Screening. 6. Currently being treated with injectable (except insulin) and/or oral antidiabetic agents with stable doses for at least 1 month prior to Screening.

  7\. HbA1c 6.5-9% (in past 8 weeks). 8. Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2. (in past 8 weeks) 9. Triglycerides \<500 mg/dL (in past 8 weeks) 10. Painful symptoms associated with OA of the knee for ≥6 months prior to Screening (NRS of 4-9 during most of the 30 days prior to enrollment).

  11\. Currently meets modified ACR criteria (clinical and radiological) for OA (Altman et al, 1986) as follows:
  1. Knee pain
  2. At least 1 of the following:

     * Stiffness \<30 minutes
     * Crepitus
  3. Osteophytes 12. Index knee pain more than 15 days over the last month (as reported by the subject).

     13\. Kellgren-Lawrence Grade 2-4. 14. Willingness to wear a CGM device uninterrupted for 24 hours per day throughout the required time during the study and comply to the correct use requirements of CGM throughout the trial and perform self BG checks as directed.

     15\. Adequate BG data collected during the pretreatment phase (Day -10 through Day -1) ≥70% data available.

     Exclusion Criteria:

     Disease-related Criteria
     1. Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease.
     2. History of infection in the index knee joint.
     3. Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening.
     4. Presence of surgical hardware or other foreign body in the index knee.
     5. Unstable joint (such as a torn anterior cruciate ligament) within 12 months of Screening.
     6. Moderate or severe kidney, liver, or thyroid disease.
     7. Glaucoma.
     8. Active cancer. Previous or Concomitant Treatment-related Criteria
     9. IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening.
     10. IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening.
     11. IV or intramuscular (IM) corticosteroids (investigational or marketed) within 3 months of Screening.
     12. Oral corticosteroids (investigational or marketed) within 1 month of Screening.
     13. Inhaled, intranasal, or topical corticosteroids (investigational or marketed) within 2 weeks of Screening.
     14. Any other IA investigational device, drug/biologic within 6 months of Screening or 5 half-lives (whichever is longer).
     15. Prior arthroscopic or open surgery of the index knee within 12 months of Screening.
     16. Planned/anticipated surgery of the index knee or any other surgery during the study period.
     17. Use of acetaminophen, or acetaminophen-containing products, from Screening through Day 14 (completion of post-treatment BG monitoring).
     18. Subjects on Coumadins with INR ≥5 will be excluded (Bashir et al, 2015) Subject-related Criteria
     19. Known hypersensitivity to any form of triamcinolone.
     20. History of sarcoidosis or amyloidosis.
     21. Active or history of malignancy within the last 3 years, except for resected basal cell carcinoma, squamous cell carcinoma of the skin, or effectively managed cervical carcinoma.
     22. Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral, or parasitic infections or ocular herpes simplex.
     23. Any infection requiring IV antibiotics within 4 weeks of Screening or infection requiring oral antibiotics within 2 weeks of Screening.
     24. History of osteomyelitis.
     25. Known or clinically suspected infection with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
     26. Requiring or likely to require treatment with corticosteroids during the study period based on subject medical history.
     27. History or active Cushing's or Addison's syndrome.
     28. Active substance abuse (drugs or alcohol), history of chronic substance abuse within the last year, or prior chronic substance abuse judged by the Investigator likely to recur during the study.
     29. Skin breakdown at the knee where the injection would take place.
     30. Use of immunomodulators, immunosuppressives, or chemotherapeutic agents within 2 years of Screening.
     31. Receipt of a live or live attenuated vaccine within 3 months of Screening.
     32. Any other clinically significant psychiatric acute or chronic medical conditions that, in the judgment of the Investigator, would preclude the use of an IA corticosteroid or NSAIDs or that could compromise subject safety, limit the subject's ability to complete or adhere to the study, and/or compromise the objectives of the study.

Where this trial is running

Kansas City, Kansas

• University of Kansas Medical Center — Kansas City, Kansas, United States (RECRUITING)

Study contacts

• Principal investigator: Neil A Segal, MD, MS — University of Kansas Medical Center
• Study coordinator: Jeannine Nilges, MD

Conditions: Osteoarthritis, Knee, Diabetes Mellitus, Type 2, Zilretta, Kenalog