Knee Osteoarthritis
Conditions
Brief summary
This research assesses the effects that Photobiomodulation Therapy (PBMT) has on Intra-articular administered Plasma-Rich Platelet (PRP) injections for Knee Osteoarthritis (KOA) treatment through evaluations of synovial and serum inflammatory and reparative biomarkers. A comparison of Physical Therapy (PT) vs PT + PRP vs PT + PBMT vs PT + PRP + PBMT for KOA treatment is made. The relationship between self-reported pain and functionality and treatment mechanisms is analyzed along with an analysis of the intersectionality between participant self-reported pain and functionality and medicine markers across treatment groups. These aims seek to inform current treatment practices in treating KOA and returning Active-Duty Service Members to duty readiness.
Detailed description
Post Traumatic Knee Osteoarthritis (PTOA) is a degenerative joint disease resulting in the loss of cartilage due to wear and tear or by an uncharacteristic force applied to the knee. This disease appears frequently in Active-Duty Service Members and is rising in prominence where over 20,000 Knee Osteoarthritis (KOA) cases were detected over a 10-year period. Current treatments such as physical therapy (PT), braces, oral pain relievers, corticosteroid, and hyaluronic acid injections for KOA only address the quality of life and the symptoms but have not demonstrated a reverse in disease progression. Studies have found that Platelet-Rich Plasma (PRP) has shown to be a promising treatment 6-12 months post procedure and may slow KOA progression. Photobiomodulation therapy (PBMT) is a non-invasive treatment option shown to reduce pain, increase function, and decrease stiffness with or without therapeutic exercises in KOA patients. In combination, PRP and PBMT may increase the recovery benefits while and potentially reduce KOA progression while seeking therapy. The exact dosage for the optimization of treatment with both PRP and PBMT still needs to be analyzed and understood. Therefore, this study will investigate four treatment arms utilizing PT, PT plus PRP, PT plus PBMT, and PT plus PRP plus PBMT. This discover based and randomized control trial will investigate the effect of PBMT and intra-articular administered PRP treatment on clinical outcomes (e.g., pain scores) and biomolecular signatures (DNA, RNA, or protein levels) in the blood or synovial spaces.The participants' intersectionality between pain, functionality, and precision medicine markers will be analyzed across treatment groups. Follow-up data in the form of questionnaires and activity logs will be collected to monitor study progression.
Interventions
OTHERPhysical Therapy
The PT treatment participants receive in this study will be standard of care; that is, the PT treatment regimen will not be standardized across study participants and/or dictated by study-specific criteria. Participants will be referred to the Physical Therapy Department at the Madigan Army Medical Center (MAMC). Number of PT treatments will be documented on a follow-up Chart Review.
BIOLOGICALPlatelet-Rich Plasma Injection
PRP injection procedures will follow current clinical recommendation and standard operating procedures. Prior to the injection, the area will be sterilely prepared and anesthetized with either ethyl chloride spray or lidocaine (limited to the cutaneous and subcutaneous layer, so as not to alter the synovial contents). Then, the participant will receive LP-PRP injection in the affected knee area under ultrasound guidance. Qualified study providers will inject 2-5cc LP-PRP using an 18-gauge 1/5-inch needle for both aspiration and subsequent injection. Study providers will select the injection portal they are most comfortable with, in order to achieve an accurate intra-articular injection. The PRP injection procedure is expected to take approximately one hour.
DEVICEPhotobiomodulation Therapy
PBMT is delivered with the LightForce® XPi 25W device through the Smart Hand Piece technology. PBMT will be delivered at 6 J/cm\^2 and applied in a circular pattern to the knee area.
Sponsors
The Geneva Foundation
Musculoskeletal Injury Rehabilitation Research for Operational Readiness
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* DEERS Eligible * Between 18-64 (Inclusive) * Civilian * Contractor * Active Duty Service Member * Knee Osteoarthritis diagnosis a) at least 3 of the following: 1. \>50 years old 2. Morning stiffness \< 30 minutes 3. Crepitus on active movements 4. Tenderness of the bony margins of the joint 5. Bony enlargement 6. No palpable warmth * Fluent in speaking and reading English * Ability to commit to study intervention and follow-up * Willing to avoid prohibited treatments while enrolled in the study (NSAIDs/COX-2 inhibitors and ASAs for 5 days prior to and 2 weeks following study injection or beginning of treatment, and oral steroids, steroid injections, and viscos supplementation) * Radiographic evidence of knee osteoarthritis as assessed by Kellgren-Lawrence grade 1 or higher
Exclusion criteria
* Current participation in other research studies for knee OA * Previous enrollment for contralateral knee * Hx of arthroscopic surgery on the study knee within the past year * Hx of arthroplasty on the study knee * Received dry needling within the past 4 weeks * Received prolotherapy (e.g. CSI or PRP injection), within past month * Recent (within the last 3 months) lower extremity injury (e.g., ankle sprain, meniscus tear or sprain, etc.) that required professional medical attention, and occurred in the ipsilateral extremity of the study knee * Confounding, coexisting pathology suspected to be the primary source of their pain \[e.g., acute meniscal tear (with mechanical symptoms), ligamentous changes (with clinical instability) or hemarthrosis\] * Current or chronic sciatica (lumbosacral radiculopathy) resulting in chronic or intermittent lower extremity pain, numbness, or tingling * Diagnosis of neuropathy affecting sensation to pain * Diagnosis of inflammatory arthropathy * Diagnosis of fibromyalgia or chronic fatigue syndrome * Hx of adverse reaction to PRP injection (either documented in the medical record or shared by the patient during screening) * Tattoo in treatment area * Diagnosis of porphyria (light induced allergy) or photosensitive eczema * Current use of medications associated with sensitivity to heat or light (e.g., amiodarone, chlorpromazine, doxycycline, hydrochlorothiazide, nalidixic acid, naproxen, piroxicam, tetracycline, thioridazine, voriconazole) * Current use of pacemaker * Hx of underlying cardiac disease * Diagnosis of autoimmune disease * Albinism * Current pregnancy or plans to become pregnant during intervention period * Hx of memory problems, dementia, and/or impaired decision-making ability * Any other serious medical conditions(s) that might preclude optimal outcome and/or interfere with participation (e.g.), intra-articular sepsis, bacteremia, fracture, joint instability, rheumatoid arthritis, osteoporosis, cancer, coagulopathy, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kellgren Lawrence Classification System (KL) | Baseline | Kellgren Lawrence Classification System (KL) will score the radiographic evidence of the participant's knee osteoarthritis. Minimum Score: Grade 0 (none): definite absence of X-ray changes of knee OA Maximum Score: Grade 4 (severe): Large osteophyte formation, joint space narrowing, definite bone end deformity Higher grades indicate a worse outcome. |
| Defense and Veterans Pain Rating Scale (DVPRS) | Baseline | Defense and Veterans Pain Rating Scale (DVPRS) will capture current pain severity. Minimum Score: 0 (no pain) Maximum Score: 10 (As bad as it could be, nothing else matters) A higher score indicates, increasing pain. |
| Single Assessment Numeric Evaluation (SANE) | Baseline | Single Assessment Numeric Evaluation (SANE) will rate the participant's knee osteoarthritis condition as a percentage from normal. Minimum Score: 0% (Abnormal) Maximum Score: 100% (Fully Normal) An increasing percentage means the closer the participant feels their knee is back to normal function. |
| Knee Injury Osteoarthritis Outcome Score (KOOS) | Baseline | Knee Injury Osteoarthritis Outcome Score (KOOS) will ask the participants questions while thinking about their injured knee symptoms in the past week. Minimum Score: None Maximum Score: Extreme On a per question basis, the participant states how significant their knee symptoms are. |
| The Veterans Rand 12 Item Health Survey (VR-12) | Baseline | The Veterans Rand 12 Item Health Survey (VR-12) asks participants about their feelings and how well they can do their usual activities. Minimum Score 1: Poor Maximum Score 1: Excellent Refers to a participant's general health. Minimum Score 2: Yes, limited a lot Maximum Score 2: No, not limited at all Refers to activity, how their health has limited them. Minimum Score 3: No, none of the time Maximum Score 3: Yes, all of the time How Physical health has that impacted accomplishments and the kind of work of other activities. Minimum Score 4: Not at all Maximum Score 4: Extremely Refers to how pain interferes with normal work. Minimum Score 5: All of the time Maximum Score 5: None of the time Refers to feeling calm, having energy, and whether they feel downhearted. Minimum Score 6: Much worse Maximum Score 6: Much better A comparison of physical health compared to a year ago and a comparison of emotional health compared to a year ago. |
| Biorepository Blood Draw for Biomarkers of Interest ADAMTS-4 &5 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 &5. |
| Biorepository Blood Draw for Biomarkers of Interest MMP 7 & 9 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7 & 9. |
| Biorepository Blood Draw for Biomarkers of Interest TGF-B | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: TGF-B. |
| Biorepository Blood Draw for Biomarkers of Interest Aggrecan | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan. |
| Biorepository Blood Draw for Biomarkers of Interest HYAL2 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2. |
| Biorepository Blood Draw for Biomarkers of Interest CRP | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP. |
| Biorepository Blood Draw for Biomarkers of Interest HA | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA. |
| Biorepository Blood Draw for Biomarkers of Interest CD14 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14. |
| Biorepository Blood Draw for Biomarkers of Interest CD16 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16. |
| Biorepository Blood Draw for Biomarkers of Interest CD64 | Baseline | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64. |
| Knee Joint Aspiration for Biomarkers of Interest CD64 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64. |
| Knee Joint Aspiration for Biomarkers of Interest CD16 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD16. |
| Knee Joint Aspiration for Biomarkers of Interest CD14 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD14. |
| Knee Joint Aspiration for Biomarkers of Interest HA | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HA. |
| Knee Joint Aspiration for Biomarkers of Interest CRP | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CRP. |
| Knee Joint Aspiration for Biomarkers of Interest HYAL2 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: HYAL2. |
| Knee Joint Aspiration for Biomarkers of Interest Aggrecan | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan. |
| Knee Joint Aspiration for Biomarkers of Interest TGF-B | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: Aggrecan. |
| Knee Joint Aspiration for Biomarkers of Interest MMP 7 & 9 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: MMP 7& 9. |
| Knee Joint Aspiration for Biomarkers of Interest ADAMTS-4 & 5 | Baseline | Synovial fluid from the knee will be extracted and stored in the biorepository. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 & 5. |
| Biorepository Blood Draw for Biomarkers of Interest CD64. | 6-week follow-up | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: CD64. |
| Biorepository Blood Draw for Biomarkers of Interest ADAMTS-4 & 5 | 6-week follow-up | 4 ml of blood collected in K2/EDTA tube, 4 ml of blood collected in heparin tube, 3 ml of blood collected in DNA/RNA tube. Once sufficient sampling has been met, batch analyses will be completed for biomarker capture including: ADAMTS-4 & 5. |
| Complete Blood Count (CBC) Analysis WBC | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of WBC. |
| Complete Blood Count (CBC) Analysis RBC | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of RBC. |
| Complete Blood Count (CBC) Analysis HGB | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of HGB. |
| Complete Blood Count (CBC) Analysis HCT | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of HCT. |
| Complete Blood Count (CBC) Analysis PLT | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of PLT. |
| Complete Blood Count (CBC) Analysis LYM% | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM%. |
| Complete Blood Count (CBC) Analysis LYM# | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM#. |
| Complete Blood Count (CBC) Analysis MON% | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of MON%. |
| Complete Blood Count (CBC) Analysis GRA% | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of GRA%. |
| Complete Blood Count (CBC) Analysis Neutrophil% | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of Neutrophil%. |
| Complete Blood Count (CBC) Analysis Eosinophil%, | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of Eosinophil%. |
| Complete Blood Count (CBC) Analysis Basophil% | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of Basophil%. |
| Complete Blood Count (CBC) Analysis MON# | Baseline | Whole blood and PRP spin analysis will be completed to analyze total blood content of MON#. |
Countries
United States
Outcome results
None listed