Effect of Steroid Injections in a Knee With Osteoarthritis

NCT01230424 | Completed Phase 4 Results DMC

• 2 other identifiers: NIH NIAMS R01-AR057802Tufts MC IRB Protocol # 9417
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

A steroid (triamcinolone) 40 mg will be compared to placebo in a randomized placebo-controlled clinical trial testing the effect of this steroid versus placebo given into the study knee joint that has osteoarthritis (OA). The knee injection will be given once every 12 weeks over two years for a total of eight knee injections. How well each participant tolerates each injection and all the injections over time will be assessed. The safety of getting a knee injection every 12 weeks will be assessed by collecting reported adverse effects, knee examinations, and clinical laboratory tests. Participants will complete questionnaires, X-ray, MRIs, and bone density tests as part of this study.

Conditions

Osteoarthritis (OA) of the Knee

Keywords

OA; Knee arthritis; MRI; Steroid

Outcome Measures

Primary Outcomes (2)

• Change in Mean Cartilage Thickness in the Index Compartment (Compartment With the Most Damage)

  Mean cartilage thickness was measured on knee MRI (Philips Achieva X-Series 3.0 Tesla scanner). Missing data were imputed.

  Baseline to 2 years

• Change in Knee Pain Severity During the Past 48 Hours From the WOMAC LK3.1 Pain Score Questionnaire.

  Pain subscale score was calculated from patient's responses on the Western Ontario and McMaster Universities Osteoarthritis Index Likert-type 3.1 Questionnaire. The questionnaire includes 24 items divided into 3 subscales, Pain, Stiffness, Physical Function. Only the Pain subscale score was used for this outcome measure. The Pain subscale consists of five items, each ranging from 0 to 4, making the total Pain subscore 0 to 20. Higher scores represent higher levels of pain, whereas lower scores represent lower levels of pain. Missing data were imputed.

  Baseline to 2 years

Secondary Outcomes (9)

• Change in Volume of Peri-articular Bone Marrow Lesions Measured on Knee MRI.

  Baseline to 2 years.

• Change in Effusion Volume Measured on Knee MRI.

  Baseline to 2 years

• Change in Area of Denudation Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).

  Baseline to 2 years

• Change in Volumetric Cartilage Damage Index (CDI) Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).

  Baseline to 2 years

• Change in Function Severity During the Past 48 Hours From the WOMAC LK3.1 Function Score Questionnaire.

  Baseline to 2 years

Study Arms (2)

Triamcinolone Acetonide

EXPERIMENTAL

40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Drug: Triamcinolone Acetonide

Sodium Chloride

PLACEBO COMPARATOR

0.9% Sodium chloride injection as Placebo will be given into the study knee once every 12 weeks for a total of 8 injections.

Drug: 0.9% Sodium Chloride Injection as Placebo

Interventions

Triamcinolone Acetonide DRUG

40 mg into the study knee joint every 12 weeks for a total of 8 injections.

Also known as: Kenalog

Triamcinolone Acetonide

0.9% Sodium Chloride Injection as Placebo DRUG

Sodium chloride injection will be given into the study knee once every 12 weeks for a total of 8 injections.

Also known as: Normal Saline for injection

Sodium Chloride

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or Male, Age ≥ 45 years
• Chronic knee discomfort based on affirmative response to the question "During the past 12 months, have you had any pain, aching, or stiffness in or around your knee(s) on most days for at least one month?"
• Baseline (Month 0) Pain score \>2 on at least one of the WOMAC weight-bearing pain questions; and total weight-bearing pain score \<8
• Tibiofemoral or patellofemoral OA on posterior-anterior weight-bearing semi-flexed or lateral knee radiographs with severity equivalent to Kellgren and Lawrence grade 2 or 3
• Evidence of synovitis on ultrasound at screening
• Clinical examination confirming knee pain or discomfort referable to the knee joint
• Prepared to discontinue NSAID(s)/analgesic(s) for 2 days prior to each assessment

You may not qualify if:

• Prior septic (study) knee joint
• Prior reconstructive surgery in the study knee
• Prior osteonecrosis (avascular necrosis of bone)
• Chronic use of oral corticosteroids; knee intra-articular corticosteroid injection within 3 months of Month 0 (baseline) visit
• Ongoing use of doxycycline, indomethacin, glucosamine and/or chondroitin; or use of these within 2 months of Screening visit
• Evidence of other inflammatory joint disease (e.g., gout, CPPD)
• Serious medical conditions or impairments that, in the view of the investigator, would obstruct their participation in the trial such as uncontrolled diabetes, uncontrolled hypertension, opiate dependency
• Plan to permanently relocate from the region, or take an extended vacation for greater than 3 months during the trial period
• Planned arthroscopy and/or arthroplasty in the study knee.
• Any contra-indication to having an MRI
• Inability to speak or comprehend English

Sponsors & Collaborators

• Tufts Medical Center: lead
• Boston University: collaborator

Study Sites (2)

Tufts Medical Center / Division of Rheumatology

Boston, Massachusetts, 02111, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (1)

• McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1967-1975. doi: 10.1001/jama.2017.5283.

  PMID: 28510679 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

Triamcinolone Acetonide; Sodium Chloride; Saline Solution; Injections

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Plan for interim analysis was eliminated with the support of the DSMB because of feasibility issues for completing cartilage measurements contemporaneously and because early trial cessation would preclude analysis of informative secondary outcomes.

Results Point of Contact

• Title: Dr. Timothy McAlindon
• Organization: Tufts Medical Center

tmcalindon@tuftsmedicalcenter.org

6176365610

Study Officials

• Timothy E. McAlindon, MD, MPH

  Tufts Medical Center / Division of Rheumatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: October 29, 2010
• Study Start: March 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: July 31, 2017
• Results First Posted: July 31, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)