Investigating Orthobiologics After PRP and Photobiomodulation for Knee Osteoarthritis

Not Applicable

Terminated

• Conditions: Knee Osteoarthritis
• Interventions: Other: Physical Therapy; Device: Photobiomodulation Therapy; Biological: Platelet-Rich Plasma Injection

• Registration Number: NCT06122116
• Lead Sponsor: Musculoskeletal Injury Rehabilitation Research for Operational Readiness

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.

Study Timeline

• Study Start: 2023-10-13
• Study First Submitted: 2023-10-26
• Study First Submitted QC: 2023-11-02
• Study First Posted: 2023-11-08
• Primary Completion: 2024-10-10
• Study Completion: 2024-10-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 33

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Physical Therapy (PT) Only	Physical Therapy	All participants will complete a standard of care PT program addressing individual strength, mobility, and flexibility deficits in both proximal and distal muscle groups. The provider may also use other modalities to address distal issues. If a participant has not been placed on profile at the time of consent, a profile may be written by the study medical provider to ensure limitation of activities, as appropriate.
PT + Photobiomodulation Treatment (PBMT)	Physical Therapy	In addition to SOC PT, the PBMT group will receive PBM treatment, as outlined below. PBM treatments will occur 3 times each week, for 3 weeks. A member of the study team will measure the treatment area according to a standard protocol and calculate the treatment time (approximately 5-20 minutes). PBMT will be delivered at 6 J/cm2 and 25W and applied in a serpentine pattern to the knee area. Participants will be asked to refrain from using perfumes or plant extracts (e.g., St. John's Wort) in the treatment area(s), as this can increase skin photosensitivity.
PT + Photobiomodulation Treatment (PBMT)	Photobiomodulation Therapy	In addition to SOC PT, the PBMT group will receive PBM treatment, as outlined below. PBM treatments will occur 3 times each week, for 3 weeks. A member of the study team will measure the treatment area according to a standard protocol and calculate the treatment time (approximately 5-20 minutes). PBMT will be delivered at 6 J/cm2 and 25W and applied in a serpentine pattern to the knee area. Participants will be asked to refrain from using perfumes or plant extracts (e.g., St. John's Wort) in the treatment area(s), as this can increase skin photosensitivity.
PT + PRP + PBMT	Photobiomodulation Therapy	In addition to SOC PT, the PRP and PBMT group will receive PRP treatment and PBMT treatments. Participants in this group will start PBMT treatments on the same day after receiving the study PRP injection. On the day of the PRP injection, the participant will be instructed to rest for 5-10 minutes prior to the PBMT application and team member will ensure the participant is comfortable not in pain. Immediately following the study injection, the team member will take care not to provide the PBMT over the injected area; however, all subsequent PBMT treatments will be delivered to the knee where the PRP was injected.
PT + Platelet-Rich Plasma (PRP)	Physical Therapy	PRP Preparation: The PRP will be prepared following standard technique by drawing 60cc blood from the participant through venipuncture and spinning the blood sample in a centrifuge (for approximately 17 minutes), adjusting for leukocyte poor-platelet rich plasma (LP-PRP). This sample will be prepared by the study provider. Any leftover blood will be safely discarded per standard protocols. A small portion of the pre-spin whole blood (approximately 1 cc) and post-spin injectant PRP (approximately 1 cc) will be sent to MAMC Department of Pathology and Laboratory Services (DPALS) for complete blood count (CBC) cytology to monitor standardization and reproducibility. This portion will be labeled by participant ID and study. De-identified hardcopy results will be obtained from MAMC DPALS, and CBC results will be reported on Appendix G (CBC Results CRF). Post-procedural instructions will be provided in a participant handout.
PT + Platelet-Rich Plasma (PRP)	Platelet-Rich Plasma Injection	PRP Preparation: The PRP will be prepared following standard technique by drawing 60cc blood from the participant through venipuncture and spinning the blood sample in a centrifuge (for approximately 17 minutes), adjusting for leukocyte poor-platelet rich plasma (LP-PRP). This sample will be prepared by the study provider. Any leftover blood will be safely discarded per standard protocols. A small portion of the pre-spin whole blood (approximately 1 cc) and post-spin injectant PRP (approximately 1 cc) will be sent to MAMC Department of Pathology and Laboratory Services (DPALS) for complete blood count (CBC) cytology to monitor standardization and reproducibility. This portion will be labeled by participant ID and study. De-identified hardcopy results will be obtained from MAMC DPALS, and CBC results will be reported on Appendix G (CBC Results CRF). Post-procedural instructions will be provided in a participant handout.
PT + PRP + PBMT	Physical Therapy	In addition to SOC PT, the PRP and PBMT group will receive PRP treatment and PBMT treatments. Participants in this group will start PBMT treatments on the same day after receiving the study PRP injection. On the day of the PRP injection, the participant will be instructed to rest for 5-10 minutes prior to the PBMT application and team member will ensure the participant is comfortable not in pain. Immediately following the study injection, the team member will take care not to provide the PBMT over the injected area; however, all subsequent PBMT treatments will be delivered to the knee where the PRP was injected.
PT + PRP + PBMT	Platelet-Rich Plasma Injection	In addition to SOC PT, the PRP and PBMT group will receive PRP treatment and PBMT treatments. Participants in this group will start PBMT treatments on the same day after receiving the study PRP injection. On the day of the PRP injection, the participant will be instructed to rest for 5-10 minutes prior to the PBMT application and team member will ensure the participant is comfortable not in pain. Immediately following the study injection, the team member will take care not to provide the PBMT over the injected area; however, all subsequent PBMT treatments will be delivered to the knee where the PRP was injected.

Primary Outcome Measures

Name	Time	Method
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	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: MMP 7 \& 9.
Biorepository Blood Draw for Biomarkers of Interest TGF-B	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: TGF-B.
Biorepository Blood Draw for Biomarkers of Interest CRP	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: CRP.
Single Assessment Numeric Evaluation (SANE)	Daily, for 6 weeks	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.
The Veterans Rand 12 Item Health Survey (VR-12)	6-week follow-up	The Veterans Rand 12 Item Health Survey (VR-12) will ask participants about how they feel and how well they are able to 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.
Knee Joint Aspiration for Biomarkers of Interest CD16	6-week follow-up	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.
Defense and Veterans Pain Rating Scale (DVPRS)	Daily, for 6 weeks	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.
Biorepository Blood Draw for Biomarkers of Interest Aggrecan	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: Aggrecan.
Knee Joint Aspiration for Biomarkers of Interest HA	6-week follow-up	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.
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 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 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%.
Knee Joint Aspiration for Biomarkers of Interest CRP	6-week follow-up	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.
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.
Knee Injury Osteoarthritis Outcome Score (KOOS)	6-week follow-up	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.
Biorepository Blood Draw for Biomarkers of Interest HYAL2	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: HYAL2.
Knee Joint Aspiration for Biomarkers of Interest CD64	6-week follow-up	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 CD14	6-week follow-up	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.
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#.
Biorepository Blood Draw for Biomarkers of Interest HA	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: HA.
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.
Biorepository Blood Draw for Biomarkers of Interest CD14	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: CD14.
Knee Joint Aspiration for Biomarkers of Interest HYAL2	6-week follow-up	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	6-week follow-up	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	6-week follow-up	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.
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.
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 LYM#	Baseline	Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM#.
Knee Joint Aspiration for Biomarkers of Interest TGF-B	6-week follow-up	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: TGF-B.
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 LYM%	Baseline	Whole blood and PRP spin analysis will be completed to analyze total blood content of LYM%.
Biorepository Blood Draw for Biomarkers of Interest CD16	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: CD16.
Knee Joint Aspiration for Biomarkers of Interest ADAMTS-4 & 5	6-week follow-up	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 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.

Trial Locations

Locations (1)

Madigan Army Medical Center; 🇺🇸 Tacoma, Washington, United States