Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Tear
Conditions
Brief summary
A potential long-term consequence of anterior cruciate ligament injuries is the development of post-traumatic osteoarthritis in the years following injury. There are no curative treatments for osteoarthritis, increasing the importance of minimizing the occurrence of post-traumatic osteoarthritis following anterior cruciate ligament injuries. Current literature has begun to indicate that biochemical changes in the knee joint cartilage, such as chondrocyte death, following injury can contribute to the development of post-traumatic osteoarthritis. The main objective of this study is to determine if an early intervention of joint aspiration and platelet rich plasma injection will positively affect the biomarkers representative of chondral degeneration in patients with anterior cruciate ligament injuries. We hypothesize that the intervention will reduce the volume of inflammatory and chondrodegenerative biomarkers following anterior cruciate ligament injury.
Detailed description
A non-surgical treatment option for the management of osteoarthritis include injectables such as corticosteroids and platelet rich plasma. These injectables work by positively affecting cartilage cells, also known as chondrocytes, and the cells of the joint lining tissue, also known as synoviocytes. Platelet rich plasma is an autologous derived blood product, i.e. a joint injectable made from the patient's own blood at the time and location of injection with simple blood centrifugation. Studies in the bench-top laboratory setting have provided in-vitro evidence that platelet rich plasma decreases synoviocyte production of metallometal proteases, an inflammatory protein with negative effects on cartilage and decreases the effects of inflammatory proteins.
Interventions
DRUGExperimental Group
Patients will receive platelet rich plasma injection two times prior to surgery.
OTHERControl Group
Patients will have their knee aspirated at their initial physician visit and at the time of surgery.
Sponsors
Andrews Research & Education Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* No history of previous traumatic ipsilateral knee injury * Bone bruise visualized on MRI * No clinical evidence of posterior cruciate ligament injury with no more than grade 1 medial or lateral collateral ligament injury
Exclusion criteria
* Patients without a palpable knee effusion * An injury occurring more than 10 days before enrollment * Previous ipsilateral knee surgery * Intra-articular cortisone or platelet rich plasma injection into either knee within 3 months of injury * Participation in another clinical drug trial within the 4 weeks before injury * A history of any inflammatory disease or immune-comprised
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | Timepoint 1: initial visit (within 10 days of injury) Timepoint 2: at the time of surgery (within 4 weeks of injury) | The presence of the Synovial Interleukin (IL) -1 Receptor Antagonist biomarker in the synovial fluid will be assessed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Group The control group will have a joint aspiration performed at an initial visit (within the first 10 days after injury), and at the time of surgery (within 4 weeks of injury).
Control Group: Patients will have their knee aspirated at their initial physician visit and at the time of surgery. | 12 |
| Experimental Group The experimental group will have a joint aspiration performed at an initial visit (within the first 10 days after injury) and receive an injection of leukocyte poor platelet rich plasma injection in their knee. At a second visit 5-12 days after the initial visit, the patient will receive a joint aspiration and platelet rich plasma injection. A final joint aspiration will be performed at the time of surgery (within 4 weeks of injury).
Experimental Group: Patients will receive platelet rich plasma injection two times prior to surgery. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Surgery postponed >5weeks | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Control Group | Experimental Group | Total |
|---|---|---|---|
| Age, Continuous | 19.4 years STANDARD_DEVIATION 8 | 20 years STANDARD_DEVIATION 6.7 | 20 years STANDARD_DEVIATION 7.7 |
| BMI | 29.1 kg/m^2 STANDARD_DEVIATION 6.8 | 22.5 kg/m^2 STANDARD_DEVIATION 4 | 26.2 kg/m^2 STANDARD_DEVIATION 6.48 |
| Height | 173 cm STANDARD_DEVIATION 11.5 | 174.6 cm STANDARD_DEVIATION 8.3 | 174.6 cm STANDARD_DEVIATION 11.63 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 16 Participants |
| Time to Surgery (days) | 16.9 days STANDARD_DEVIATION 6.8 | 27 days STANDARD_DEVIATION 13.1 | 20.74 days STANDARD_DEVIATION 9.34 |
| Weight | 87.6 kg STANDARD_DEVIATION 26.7 | 68.5 kg STANDARD_DEVIATION 12.8 | 80.8 kg STANDARD_DEVIATION 21.56 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 9 |
| other Total, other adverse events | 0 / 8 | 0 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 |
Outcome results
Primary
Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration
The presence of the Synovial Interleukin (IL) -1 Receptor Antagonist biomarker in the synovial fluid will be assessed.
Time frame: Timepoint 1: initial visit (within 10 days of injury) Timepoint 2: at the time of surgery (within 4 weeks of injury)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-6 Timepoint 1 | 7668.6 pg/ml | Standard Deviation 4092.9 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-1ß Timepoint 1 | 13.8 pg/ml | Standard Deviation 4.1 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-1ß Timepoint 2 | 9.9 pg/ml | Standard Deviation 4.9 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-10 Timepoint 1 | 53.1 pg/ml | Standard Deviation 16.4 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-10 Timepoint 2 | 36.1 pg/ml | Standard Deviation 20.3 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-6 Timepoint 2 | 3940.2 pg/ml | Standard Deviation 3809.2 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | GM- CSF Timepoint 1 | 20.6 pg/ml | Standard Deviation 7.1 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | GM- CSF Timepoint 2 | 16 pg/ml | Standard Deviation 10.1 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-5 Timepoint 1 | 30.6 pg/ml | Standard Deviation 16.7 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-5 Timepoint 2 | 27.9 pg/ml | Standard Deviation 23.3 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IFN-γ Timepoint 1 | 2.5 pg/ml | Standard Deviation 1.1 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IFN-γ Timepoint 2 | 2.6 pg/ml | Standard Deviation 1.5 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | TNF-⍺ Timepoint 1 | 11.2 pg/ml | Standard Deviation 7 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | TNF-⍺ Timepoint 2 | 10.4 pg/ml | Standard Deviation 9.1 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-2 Timepoint 1 | 29.2 pg/ml | Standard Deviation 24.9 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-2 Timepoint 2 | 32.7 pg/ml | Standard Deviation 32.5 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-4 Timepoint 1 | 278.2 pg/ml | Standard Deviation 144.4 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-4 Timepoint 2 | 234.5 pg/ml | Standard Deviation 161.6 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-8 Timepoint 1 | 315.1 pg/ml | Standard Deviation 80.3 |
| Control Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-8 Timepoint 2 | 124.8 pg/ml | Standard Deviation 49.7 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-4 Timepoint 2 | 200.2 pg/ml | Standard Deviation 167.7 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-6 Timepoint 1 | 8650.8 pg/ml | Standard Deviation 3983.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IFN-γ Timepoint 1 | 4.0 pg/ml | Standard Deviation 1.7 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-1ß Timepoint 1 | 16 pg/ml | Standard Deviation 4.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-2 Timepoint 2 | 28.6 pg/ml | Standard Deviation 25.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-1ß Timepoint 2 | 7.5 pg/ml | Standard Deviation 4.5 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IFN-γ Timepoint 2 | 1.7 pg/ml | Standard Deviation 1.3 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-10 Timepoint 1 | 64.3 pg/ml | Standard Deviation 21.4 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-8 Timepoint 2 | 222.6 pg/ml | Standard Deviation 113.4 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-10 Timepoint 2 | 31.7 pg/ml | Standard Deviation 19.2 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | TNF-⍺ Timepoint 1 | 21.6 pg/ml | Standard Deviation 9.5 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-6 Timepoint 2 | 2196.2 pg/ml | Standard Deviation 2994.2 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-4 Timepoint 1 | 398.5 pg/ml | Standard Deviation 189.4 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | GM- CSF Timepoint 1 | 25.3 pg/ml | Standard Deviation 9.1 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | TNF-⍺ Timepoint 2 | 10.9 pg/ml | Standard Deviation 7.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | GM- CSF Timepoint 2 | 12.4 pg/ml | Standard Deviation 9.5 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-8 Timepoint 1 | 1295.2 pg/ml | Standard Deviation 1075.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-5 Timepoint 1 | 48.8 pg/ml | Standard Deviation 23.9 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-2 Timepoint 1 | 54.6 pg/ml | Standard Deviation 34.3 |
| Experimental Group | Change in Synovial Interleukin (IL) -1 Receptor Antagonist Concentration | IL-5 Timepoint 2 | 24.7 pg/ml | Standard Deviation 19.7 |