Knee Osteoarthritis
Conditions
Keywords
Osteoarthritis, Platelet-Rich Plasma, Intra-articular, Injection
Brief summary
The purpose of this study is to test whether the platelet-rich plasma (PRP) intra-articular injection therapy is effective as an alternative treatment option in patients with mild knee osteoarthritis within a controlled randomized study compared to first line treatment acetaminophen. The investigators will evaluate patients outcome in level of pain, knee function and quality of life before the treatment and at 6, 12 and 24 weeks follow up. The study will be complemented with in vitro experiments of human osteoarthritic cartilage explants culture (treated with PRP) for histological and gene expression assays. PRP intra-articular injections therapy is effective in patients with mild knee osteoarthritis by modifying the biochemical joint environment and cartilage regeneration capability.
Detailed description
This is a randomized controled study. Patients enroled in the study will be divided into two groups (calculated n=30 per group). One group will be treated with acetaminophen (500 mg/8 h) for 6 weeks, the experimental group will receive a total of 3 intra-articular injections of PRP, one injection every 2 weeks. The intake of any other analgesic or anti-inflammatory drug will be prohibited in patients from two groups. For those who received the infiltrations, the procedure consist of a 27-mL venous blood sample in 6 vacutainer tubes with sodium citrate 0.109 M for each injection. Samples are gently agitated to ensure mixing the anticoagulant with the blood. An extra tube with anticoagulated EDTA blood is obtained for initial platelet count. Blood samples are centrifuged for 10 minutes at 1800 rpm to separate the erythrocyte layer. The upper plasma layer is carefully collected in a new sterile propylene tube trying not to remove the leukocyte layer. Plasma from all tubes is centrifuged again for 12 minutes at 3400 rpm to obtain a two-part plasma: the upper part consisting on platelet-poor plasma and lower part consisting of platelet-rich plasma (PRP). The platelet-poor plasma is discarded to obtain a final volume of 3 mL. This volume, consisting of PRP, is mixed carefully through pipetting to resuspend platelets and it was then transferred to a new sterile glass tube. An aliquot of the final PRP is sent to the laboratory for platelet count. All open handling sample procedures are performed within a high-efficiency particulate air-filtered laminar flow hood. Application of injections is carry out after disinfection of skin in the knee joint area. After local anesthesia with lidocaine chlorohydrate, platelets are activated using 10% calcium gluconate solution and the liquid PRP is injected in a sterile condition using a 22 G needle. The needle is inserted using the superolateral approach in an angle of approximately 45°. Patients from PRP group will be asked to flex and extend their knees immediately after injection so that PRP could distribute adequately across the joint space. After 5-10 minutes of observation the patients are sent home with written indications including to have relative rest 24 to 48 hours after the injection, the use of cold therapy for 15 minutes three times a day and 500 mg of acetaminophen in case of pain and inflammation. The use of NSAIDs or any steroids is prohibited. All the patients will be evaluated before the beginning of their respective treatment and at 6, 12 and 24 weeks after. Three different scales are used to evaluate clinical outcome, the VAS (Visual Analog Scale) that scores pain level, the WOMAC (Western Ontario and McMaster Universities Arthritis Index) which assesses pain, articular stiffness and functional limitation, and the Spanish (México) version of the SF-12 (Short Form-12) for assessment of quality of life.
Interventions
PROCEDUREIntra-articular injection of PRP
Patients from this arm will receive 3 intra-articular knee injections of autologous platelet-rich plasma, one injection every two weeks (6 weeks total).
DRUGAcetaminophen
Patients from this arm will receive a dosis of acetaminophen (500 mg/8 hours) while PRP treatment lasts (6 weeks total).
Sponsors
Hospital Universitario Dr. Jose E. Gonzalez
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Older than 18 years old * Patients who haven't received steroids injection or medical treatment 1 month before the study * Patients with knee osteoarthritis grade I and II (Kellgren-Lawrence scale) * Indistinct gender * Patients who accept to participate in the study with previous signed informed consent
Exclusion criteria
* Patients with knee osteoarthritis grade III and IV (Kellgren-Lawrence scale) * Patients with prosthesis * Pregnancy * Patients with rheumatic diseases * Patients with diabetes, hepatic diseases, coagulopathy, cardiovascular diseases, immunosuppression, infections * Patients taking anticoagulants * Patients with concentrations of hemoglobin under 11 g/dL and platelets under 150,000/uL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | 0 weeks | The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analog Scale (VAS) | 0-24 weeks | The visual analog scale (VAS) is a psychometric response scale which measures subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their current level of pain by indicating a position along a continuous line of 10 cm. Subject is asked: on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable, what you rate your current pain? |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in SF-12v2 Health Survey | 0 weeks | The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. |
Countries
Mexico
Participant flow
Recruitment details
Patients diagnosed with degenerative osteoarthritis were recruited from May 2013 to November 2015 in the Service of Orthopedics and Traumatology at the University Hospital Dr. José Eleuterio González of the Autonomous University of Nuevo León in Monterrey, México.
Pre-assignment details
Only patients meeting inclusion criteria were assigned to a group (radiographic grade I and II osteoarthritis, mainly). Importantly, patients with previous surgical interventions, with concomitant diseases or with Hb values of \<11 g/dL and platelet values of \<150,000/µL were excluded prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| Acetaminophen Patients from this arm will receive a dosis of acetaminophen (500 mg/8 hours) during 6 weeks. | 32 |
| Intra-articular Injection of PRP Intra-articular injection of PRP: Patients from this arm will receive 3 intra-articular knee injections of autologous platelet-rich plasma, one injection every two weeks (6 weeks treatment). | 33 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 6 |
Baseline characteristics
| Characteristic | Acetaminophen | Total | Intra-articular Injection of PRP |
|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 11.4 | 56.4 years STANDARD_DEVIATION 9.8 | 57.2 years STANDARD_DEVIATION 8.1 |
| Body Mass Index (BMI) | 29.5 kg/m2 STANDARD_DEVIATION 3.8 | 30.9 kg/m2 STANDARD_DEVIATION 5 | 32.2 kg/m2 STANDARD_DEVIATION 6.2 |
| Grade of Osteoarthritis Kellgren-Lawrence Grade I | 12 participants | 23 participants | 11 participants |
| Grade of Osteoarthritis Kellgren-Lawrence Grade II | 20 participants | 42 participants | 22 participants |
| Sex: Female, Male Female | 20 Participants | 42 Participants | 22 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 11 Participants |
| Visual Analog Scale (VAS) | 5.9 cm STANDARD_DEVIATION 2.2 | 5.4 cm STANDARD_DEVIATION 2.3 | 4.9 cm STANDARD_DEVIATION 2.4 |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) | 35.5 units on a scale STANDARD_DEVIATION 19 | 35.6 units on a scale STANDARD_DEVIATION 19.3 | 35.7 units on a scale STANDARD_DEVIATION 19.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 4 / 33 |
| serious Total, serious adverse events | 0 / 32 | 0 / 33 |
Outcome results
Primary
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (12 weeks) | 2.2 units on a scale | Standard Deviation 2.2 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (12 weeks) | 5.7 units on a scale | Standard Deviation 4.1 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (12 weeks) | 18.4 units on a scale | Standard Deviation 13.1 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (12 weeks) | 26.3 units on a scale | Standard Deviation 17.8 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (12 weeks) | 12.0 units on a scale | Standard Deviation 10.6 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (12 weeks) | 0.9 units on a scale | Standard Deviation 1.3 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (12 weeks) | 8.1 units on a scale | Standard Deviation 7.2 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (12 weeks) | 2.7 units on a scale | Standard Deviation 2.4 |
Primary
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (24 weeks) | 1.9 units on a scale | Standard Deviation 1.9 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (24 weeks) | 5.3 units on a scale | Standard Deviation 3.9 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (24 weeks) | 16.7 units on a scale | Standard Deviation 13.3 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (24 weeks) | 23.5 units on a scale | Standard Deviation 18.4 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (24 weeks) | 11.7 units on a scale | Standard Deviation 10 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (24 weeks) | 0.8 units on a scale | Standard Deviation 1.1 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (24 weeks) | 7.9 units on a scale | Standard Deviation 7.7 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (24 weeks) | 2.9 units on a scale | Standard Deviation 2.2 |
Primary
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 0 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (0 weeks) | 3.0 units on a scale | Standard Deviation 2.1 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (0 weeks) | 8.0 units on a scale | Standard Deviation 4.3 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (0 weeks) | 24.4 units on a scale | Standard Deviation 13.7 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (0 weeks) | 35.5 units on a scale | Standard Deviation 19 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (0 weeks) | 35.7 units on a scale | Standard Deviation 19.5 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (0 weeks) | 2.9 units on a scale | Standard Deviation 2 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (0 weeks) | 25.3 units on a scale | Standard Deviation 14.3 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (0 weeks) | 7.4 units on a scale | Standard Deviation 4 |
Primary
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC)
The WOMAC evaluation will be performed on patients who received the treatment at 0, 6, 12, 24 weeks after treatment is finished. The WOMAC measures five items for pain (score range 0-20), two for stiffness (score range 0-8), and 17 for functional limitation (score range 0-68). A total WOMAC score is created by summing the items for all three subscales (score range 0-96). Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (6 weeks) | 2.3 units on a scale | Standard Deviation 1.8 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (6 weeks) | 5.8 units on a scale | Standard Deviation 2.9 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (6 weeks) | 18.2 units on a scale | Standard Deviation 12 |
| Acetaminophen | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (6 weeks) | 26.2 units on a scale | Standard Deviation 16 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Total score (6 weeks) | 12.8 units on a scale | Standard Deviation 11 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Stiffness (6 weeks) | 1.1 units on a scale | Standard Deviation 1.1 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Functional capacity (6 weeks) | 8.7 units on a scale | Standard Deviation 8 |
| Intra-articular Injection of PRP | Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) | Pain (6 weeks) | 3.1 units on a scale | Standard Deviation 2.6 |
Secondary
Change in Visual Analog Scale (VAS)
The visual analog scale (VAS) is a psychometric response scale which measures subjective characteristics or attitudes that cannot be directly measured. When responding to a VAS item, respondents specify their current level of pain by indicating a position along a continuous line of 10 cm. Subject is asked: on a scale of 0 to 10, with 0 being no pain and 10 being the worst pain imaginable, what you rate your current pain?
Time frame: 0-24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in Visual Analog Scale (VAS) | VAS (0 weeks) | 5.9 Centimeters | Standard Deviation 2.2 |
| Acetaminophen | Change in Visual Analog Scale (VAS) | VAS (6 weeks) | 3.8 Centimeters | Standard Deviation 2.2 |
| Acetaminophen | Change in Visual Analog Scale (VAS) | VAS (12 weeks) | 4.1 Centimeters | Standard Deviation 2.6 |
| Acetaminophen | Change in Visual Analog Scale (VAS) | VAS (24 weeks) | 3.7 Centimeters | Standard Deviation 2.7 |
| Intra-articular Injection of PRP | Change in Visual Analog Scale (VAS) | VAS (24 weeks) | 2.2 Centimeters | Standard Deviation 2.1 |
| Intra-articular Injection of PRP | Change in Visual Analog Scale (VAS) | VAS (0 weeks) | 4.9 Centimeters | Standard Deviation 2.4 |
| Intra-articular Injection of PRP | Change in Visual Analog Scale (VAS) | VAS (12 weeks) | 1.9 Centimeters | Standard Deviation 2 |
| Intra-articular Injection of PRP | Change in Visual Analog Scale (VAS) | VAS (6 weeks) | 1.9 Centimeters | Standard Deviation 1.6 |
Other Pre-specified
Change in SF-12v2 Health Survey
The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: 0 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in SF-12v2 Health Survey | Mental Component Summary | 50.8 units on a scale | Standard Deviation 9.9 |
| Acetaminophen | Change in SF-12v2 Health Survey | Physical Component Summary | 37.7 units on a scale | Standard Deviation 9.3 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Mental Component Summary | 44.2 units on a scale | Standard Deviation 11.8 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Physical Component Summary | 38.0 units on a scale | Standard Deviation 8 |
Other Pre-specified
Change in SF-12v2 Health Survey
The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in SF-12v2 Health Survey | Mental Component Summary | 49.8 units on a scale | Standard Deviation 9.3 |
| Acetaminophen | Change in SF-12v2 Health Survey | Physical Component Summary | 41.1 units on a scale | Standard Deviation 9.9 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Mental Component Summary | 55.4 units on a scale | Standard Deviation 8.7 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Physical Component Summary | 47.6 units on a scale | Standard Deviation 7.9 |
Other Pre-specified
Change in SF-12v2 Health Survey
The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in SF-12v2 Health Survey | Mental Component Summary | 50.7 units on a scale | Standard Deviation 8.7 |
| Acetaminophen | Change in SF-12v2 Health Survey | Physical Component Summary | 41.7 units on a scale | Standard Deviation 8.5 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Mental Component Summary | 55.9 units on a scale | Standard Deviation 7.9 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Physical Component Summary | 48.8 units on a scale | Standard Deviation 7.9 |
Other Pre-specified
Change in SF-12v2 Health Survey
The Spanish (Mexico) version of the SF-12v2 Health Survey uses 12 questions to measure functional health and well-being from the patient's point of view. All 12 items from the survey can be summarized in two main domains (physical and mental health). Physical and Mental Health Composite Scores (PCS and MCS) are computed using the scores of 12 questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen | Change in SF-12v2 Health Survey | Mental Component Summary | 52.3 units on a scale | Standard Deviation 7.2 |
| Acetaminophen | Change in SF-12v2 Health Survey | Physical Component Summary | 41.4 units on a scale | Standard Deviation 7.4 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Mental Component Summary | 54.3 units on a scale | Standard Deviation 7.6 |
| Intra-articular Injection of PRP | Change in SF-12v2 Health Survey | Physical Component Summary | 49.9 units on a scale | Standard Deviation 8.1 |