Osteoarthritis (OA) of the KneePhase 4NCT01230424
Effect of Steroid Injections in a Knee With Osteoarthritis
A Phase 4 study testing Triamcinolone Acetonide in people with Osteoarthritis (OA) of the Knee, run by Tufts Medical Center at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Osteoarthritis (OA) of the Knee
- What is being tested?
- Triamcinolone Acetonide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2011to Jan 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tufts Medical Center / Division of Rheumatology
Boston, Massachusetts, 02111
Tufts Medical Center
Boston, Massachusetts, 02111
About this study
Official title: Effect of Intra-articular Steroids on Structural Progression of Knee OA: A Randomized Controlled Trial
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.
Read the detailed description
This study was a two-year stratified and block-randomized double-blind, placebo controlled clinical trial of the effect of intra-articular triamcinolone 40 mg injectable suspension, administered every 3 months over two years (for a total of 8 doses). The randomization was stratified by the baseline radiographic severity of knee OA (Kellgren and Lawrence grade of 2 or 3) and gender. An interim analysis would have been conducted after the first half of participants has completed the trial. This interim analysis would have allowed the trial to be stopped early for either success or futility, or allow the trial to continue if neither success nor futility has been established. However, the 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. The primary structural outcome objective in this study was cartilage volume loss; secondary structural outcomes included peri-articular bone marrow lesions (BML), tibial peri-articular bone density ratio (paBMD). The primary clinical outcome objective was the pain domain of the WOMAC© LK3.1; secondary clinical outcomes included WOMAC© LK3.1 stiffness and function scores and physical function tests.
- Conditions
- Osteoarthritis (OA) of the Knee
- Being tested
- Triamcinolone Acetonide, 0.9% Sodium Chloride Injection as Placebo
- Keywords
- OA, Knee arthritis, MRI, Steroid
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Triamcinolone AcetonideDrug
Also called Kenalog
40 mg into the study knee joint every 12 weeks for a total of 8 injections.
0.9% Sodium Chloride Injection as PlaceboDrug
Also called Normal Saline for injection
Sodium chloride injection will be given into the study knee once every 12 weeks for a total of 8 injections.
| Study group | Role | What they receive |
|---|---|---|
| Triamcinolone Acetonide | Experimental | 40 mg into the study knee joint every 12 weeks for a total of 8 injections. Receives: 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. Receives: Drug: 0.9% Sodium Chloride Injection as Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline to 2 years
Secondary outcomes (9)
Change in Volume of Peri-articular Bone Marrow Lesions Measured on Knee MRI.
Change in volume of peri-articular bone marrow lesions measured on knee MRI on the log scale. Missing data were imputed.
Measured: Baseline to 2 years.
Change in Effusion Volume Measured on Knee MRI.
Change in effusion volume measured on knee MRI on the log scale. Missing data were imputed.
Measured: Baseline to 2 years
Change in Area of Denudation Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
Change in area of denudation measured on knee MRI in the index compartment (compartment with the most damage). Missing data were imputed.
Measured: Baseline to 2 years
Change in Volumetric Cartilage Damage Index (CDI) Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
Change in volumetric cartilage damage index (CDI) measured on knee MRI in the index compartment (compartment with the most damage). Missing data were imputed.
Measured: Baseline to 2 years
Change in Function Severity During the Past 48 Hours From the WOMAC LK3.1 Function Score Questionnaire.
Physical Function 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 Physical Function subscale score was used for this outcome measure. The Physical Function subscale consists of 17 items, each ranging from 0 to 4, making the total Function subscore 0 to 68. Higher scores represent higher levels of difficulty performing daily activities, whereas lower scores represent lower levels of difficulty performing daily activities.
Missing data were imputed.
Measured: Baseline to 2 years
Change in Knee Stiffness During the Past 48 Hours From the WOMAC LK3.1 Stiffness Score Questionnaire.
Stiffness 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 Stiffness subscale score was used for this outcome measure. The Stiffness subscale consists of two items, each ranging from 0 to 4, making the total Stiffness subscore 0 to 8. Higher scores represent higher levels of stiffness, whereas lower scores represent lower levels of stiffness.
Missing data were imputed.
Measured: Baseline to 2 years
Change in Patient's Global Assessment (Visual Analogue Scale).
The response to the question, "Considering all the ways your knee affects you, how much pain are you having today?", was measured and the change in the scoring was evaluated. The Patient's Global Assessment (PGA) is measured on a scale of 0 to 100 millimeters. Higher scores represent a higher level of disease activity or a worse global health. Missing data were imputed.
Measured: Baseline to 2 years
Change in Time to Complete a Twenty-meter Walk.
Change in time (seconds) to complete a twenty-meter walk. Missing data were imputed.
Measured: Baseline to 2 years
Change in Time to Complete 5 Chair Stands.
Change in time (seconds) to complete 5 chair stands. Missing data were imputed.
Measured: Baseline to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2010 (estimated)
- Study startMar 2011
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis (OA) of the KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Boston University
- Responsible party
- Sponsor
- Investigators
- Timothy E. McAlindon, MD, MPH, Principal investigator, Tufts Medical Center / Division of Rheumatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01230424
- Sponsor's protocol ID
- NIH NIAMS R01-AR057802
- Other IDs
- Tufts MC IRB Protocol # 9417
- Status last verified
- Jun 2017
- First submitted
- 27 Oct 2010
- Last updated
- 31 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 28510679
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Intra-articular Steroids on Structural Progression of Knee OA: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01230424
- Acronym / sponsor ID
- NIH NIAMS R01-AR057802
- Conditions
- Osteoarthritis (OA) of the Knee
- Keywords
- OA, Knee arthritis, MRI, Steroid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- Boston University
- Study start
- Mar 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 29 Oct 2010 (estimated)
- Results
- Posted 31 Jul 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study was a two-year stratified and block-randomized double-blind, placebo controlled clinical trial of the effect of intra-articular triamcinolone 40 mg injectable suspension, administered every 3 months over two years (for a total of 8 doses). The randomization was stratified by the baseline radiographic severity of knee OA (Kellgren and Lawrence grade of 2 or 3) and gender. An interim analysis would have been conducted after the first half of participants has completed the trial. This interim analysis would have allowed the trial to be stopped early for either success or futility, or allow the trial to continue if neither success nor futility has been established. However, the 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. The primary structural outcome objective in this study was cartilage volume loss; secondary structural outcomes included peri-articular bone marrow lesions (BML), tibial peri-articular bone density ratio (paBMD). The primary clinical outcome objective was the pain domain of the WOMAC© LK3.1; secondary clinical outcomes included WOMAC© LK3.1 stiffness and function scores and physical function tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Triamcinolone Acetonide | Experimental | Drug: Triamcinolone Acetonide40 mg into the study knee joint every 12 weeks for a total of 8 injections. |
| Sodium Chloride | Placebo comparator | Drug: 0.9% Sodium Chloride Injection as Placebo0.9% Sodium chloride injection as Placebo will be given into the study knee once every 12 weeks for a total of 8 injections. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Triamcinolone AcetonideAlso: Kenalog40 mg into the study knee joint every 12 weeks for a total of 8 injections. | Drug | Triamcinolone Acetonide |
| 0.9% Sodium Chloride Injection as PlaceboAlso: Normal Saline for injectionSodium chloride injection will be given into the study knee once every 12 weeks for a total of 8 injections. | Drug | Sodium Chloride |
Primary outcome
Change in Mean Cartilage Thickness in the Index Compartment (Compartment With the Most Damage)
Time frame: Baseline to 2 years
Mean cartilage thickness was measured on knee MRI (Philips Achieva X-Series 3.0 Tesla scanner). Missing data were imputed.
Change in Knee Pain Severity During the Past 48 Hours From the WOMAC LK3.1 Pain Score Questionnaire.
Time frame: Baseline to 2 years
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.
9 secondary outcomes
Change in Volume of Peri-articular Bone Marrow Lesions Measured on Knee MRI.
Time frame: Baseline to 2 years.
Change in Effusion Volume Measured on Knee MRI.
Time frame: Baseline to 2 years
Change in Area of Denudation Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
Time frame: Baseline to 2 years
Change in Volumetric Cartilage Damage Index (CDI) Measured on Knee MRI in the Index Compartment (Compartment With the Most Damage).
Time frame: Baseline to 2 years
Change in Function Severity During the Past 48 Hours From the WOMAC LK3.1 Function Score Questionnaire.
Time frame: Baseline to 2 years
Change in Knee Stiffness During the Past 48 Hours From the WOMAC LK3.1 Stiffness Score Questionnaire.
Time frame: Baseline to 2 years
Change in Patient's Global Assessment (Visual Analogue Scale).
Time frame: Baseline to 2 years
Change in Time to Complete a Twenty-meter Walk.
Time frame: Baseline to 2 years
Change in Time to Complete 5 Chair Stands.
Time frame: Baseline to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28510679McAlindon 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy E. McAlindon, MD, MPH principal investigator
Tufts Medical Center / Division of Rheumatology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Triamcinolone Acetonide in people with Osteoarthritis (OA) of the Knee, run by Tufts Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Mean Cartilage Thickness in the Index Compartment (Compartment With the Most Damage) (time frame: Baseline to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01230424, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2017.