Injection Site Diversity Influences HA Distribution and Clinical Results in CP and KOA

Study Overview
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Brief Summary
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In order to investigate the difference of intra-articular hyaluronate's distribution and compare the clinical outcomes of viscosupplementation for mild-to-moderate knee osteoarthritis (mKOA) between the anteromedial (AM) and medial midpatellar (MMP) approach groups. This study included two parts, cadaver study (n=64) and random controlled trial (n=100). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale in the cadaver study. The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index and the follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections in the random controlled trial.

Official Title
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Injection Site Diversity Influences Sodium Hyaluronate Distribution and Its Clinical Results in Management of Chondromalacia Patellae and Knee Osteoarthritis: A Preliminary, Multi-central, Randomize-controlled Serial Trial

Conditions
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Hyaluronan, Osteoarthritis, Knee

Intervention / Treatment
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* Procedure: medial midpatellar (MMP) portal
* Procedure: anteromedial (AM) portal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic unilateral mild-to-moderate knee osteoarthritis (mKOA) that were defined by the American College of Rheumatology criteria Kellgren-Lawrence grade 2 or 3 Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (Likert version 3.1) pain subscale reached 10 or greater Exclusion Criteria: Pregnancy, acute fracture, rheumatoid arthritis, gouty arthritis, traumatic arthritis, inflammatory arthritis Oral Celebrex within 2 weeks, HA and lidocaine allergy, intra-articular injection of HA or corticosteroid to the target knee within the past 6 months Surgery in the target knee within the past 6 months, OA of the target knee with K-L grade 4 Active liver and renal disease, cardiovascular and cerebrovascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 64 osteoarthritic knees of cadavers were randomly assigned to two groups: the anteromedial (AM) group (n=32) and the medial midpatellar (MMP) group (n=32). 100 patients with unilateral mKOA were enrolled and randomly divided into two groups according to the injection portal of HA: the AM group (n=50) and the MMP group (n=50).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AM groups in cadavers study<br>32 osteoarthritic knees of cadavers were randomly assigned to the AM group (injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale. | Procedure: anteromedial (AM) portal<br>* injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion<br>|
| Experimental: MMP groups in cadavers study<br>32 osteoarthritic knees of cadavers were randomly assigned to the MMP group (injection medial under horizontal patella midline was administrated with the lower limb extension). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale. | Procedure: medial midpatellar (MMP) portal<br>* injection medial under horizontal patella midline was administrated with the lower limb extension<br>|
| Experimental: AM groups in random controlled trial<br>50 patients with unilateral mKOA were enrolled and randomly into the AM group (injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion).The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index. The follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections. | Procedure: anteromedial (AM) portal<br>* injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion<br>|
| Experimental: MMP groups in random controlled trial<br>50 patients with unilateral mKOA were enrolled and randomly into the MMP group (injection medial under horizontal patella midline was administrated with the lower limb extension).The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index. The follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections. | Procedure: medial midpatellar (MMP) portal<br>* injection medial under horizontal patella midline was administrated with the lower limb extension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | baseline before the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 1 week after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 2 weeks after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 3 weeks after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 4 weeks after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 5 weeks after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 14 weeks after the first injection | 
| WOMAC (Likert version 3.1) | WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively. | 24 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | baseline before the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 1 week after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 2 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 3 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 4 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 5 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 14 weeks after the first injection | 
| Lequesne index | The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95. | 24 weeks after the first injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Viscosupplementation, Hyaluronate, Distribution, Knee osteoarthritis, Injection approach