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This is a Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis
This study will look at blinded standard of care (SOC) steroid injection vs. amniotic fluid injection (pAF) to treat and reduce osteoarthritis (OA) inflammation and pain. The main objectives of this study are to establish the safety and tolerability of allogeneic intra-articular pAF injections. Secondary objectives include pain levels and functional outcome scoring in patients over a 12 month time frame.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amniotic Fluid Injection | Experimental | Amniotic Fluid Injection, 3ml, one time dose. |
|
| Standard of Care Steroid Injection | Active Comparator | Corticosteroids, 3ml, one time dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amniotic Fluid Injection | Biological | Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis |
|
| Measure | Description | Time Frame |
|---|---|---|
| Repeat Allogeneic Intra-articular Injection Within 6 Months. | Participants in both the SOC and pAF treatment arms may require and/or request rescue medication (i.e. SOC injection) at any time and will be given per PI discretion as part of standard of care. The clinicians will not know which study arm the study participant is in but will treat the participant with the SOC injection. This information will be documented and collected in the Electronic Medical Record (EMR), as well as the study's electronic data capture system. Participants will not be given any additional pAF injections throughout the study period. The participant will continue to be treated with SOC injections as needed. The outcome will be an indicator of whether or not a subject received a rescue medication within 6 months. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | Knee Injury and Osteoarthritis Outcome Score (KOOS) [assessment of joint symptoms, pain, and function on a scale from 0 to 100]. With higher scores representing better symptoms, pain and function. | 6 months |
| Visual Analog Scale for Pain (VAS Pain) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Treatment Emergent Adverse Events (AEs) Directly Related to the Injection. | One adverse event potentially related to the study injection (edema in lower extremity and foot, which resolved) was reported in the Amniotic Fluid treatment group, while no adverse events related to the injection were reported in the corticosteroid treatment group. | 1 day, 2 days, 1 month, 3 months, 6 months, 12 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Petron, MD | University of Utah Orthopaedic Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Utah Orthopedic Center | Salt Lake City | Utah | 84108 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19950287 | Background | Kotlarz H, Gunnarsson CL, Fang H, Rizzo JA. Insurer and out-of-pocket costs of osteoarthritis in the US: evidence from national survey data. Arthritis Rheum. 2009 Dec;60(12):3546-53. doi: 10.1002/art.24984. | |
| 15861199 | Background | Underwood MA, Gilbert WM, Sherman MP. Amniotic fluid: not just fetal urine anymore. J Perinatol. 2005 May;25(5):341-8. doi: 10.1038/sj.jp.7211290. |
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If the patient is found to be eligible for the study, research staff will approach the patient for informed consent. Patients with bi-lateral knee OA can participate but only one knee will receive the study treatment. The treating physician/principal investigator and the patient will discuss which knee should be treated with a study injection.
Patients will be screened and consented at the University of Utah Orthopedic Center and all participating sub-investigator's clinics when they come for a standard of care physical exam. During this exam, the patient will be asked about their health and lifestyle, medical history, and current medications. As part of the SOC physical exam, the patient will also have standard of care pre-treatment x-rays, neurological assessment, and a diagnosis of mild to severe OA in the knee joint assessment.
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| ID | Title | Description |
|---|---|---|
| FG000 | pAF Injection | For the processed Amniotic Fluid (pAF) injection, the pAF injectate is prepared. The skin is prepped with Chloraprep. The skin is anesthetized using a freezing spray. 3 mLs of the pAF injectable solution is injected into the intra articular space of the knee. Ultrasound guidance will be used for all study injections. |
| FG001 | Corticosteroid Injection | For the Corticosteroid injection, the skin is prepped with Chloraprep. The skin is anesthetized using a freezing spray. Then a mixture of 1 mL of Kenalog (corticosteroid) and 2 mL of ropivacaine is injected into intra-articular space of the knee. Ultrasound guidance will be used for all study injections. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Corticosteroid Injection | For the Corticosteroid injection, the skin is prepped with Chloraprep. The skin is anesthetized using a freezing spray. Then a mixture of 1 mL of Kenalog (corticosteroid) and 2 mL of ropivacaine is injected into intra-articular space of the knee. Ultrasound guidance will be used for all study injections. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Repeat Allogeneic Intra-articular Injection Within 6 Months. | Participants in both the SOC and pAF treatment arms may require and/or request rescue medication (i.e. SOC injection) at any time and will be given per PI discretion as part of standard of care. The clinicians will not know which study arm the study participant is in but will treat the participant with the SOC injection. This information will be documented and collected in the Electronic Medical Record (EMR), as well as the study's electronic data capture system. Participants will not be given any additional pAF injections throughout the study period. The participant will continue to be treated with SOC injections as needed. The outcome will be an indicator of whether or not a subject received a rescue medication within 6 months. | Posted | Count of Participants | Participants | 6 months |
|
From enrollment, to 12 months
Adverse events were monitored throughout the study and recorded in an adverse event log. Participants were assessed at scheduled study visits and through follow-up communications. All serious adverse events observed during the study are reported, regardless of their relationship to study participation. All non-serious adverse events that exceeded a 5% frequency threshold within any study arm are reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Amniotic Fluid Injection | Amniotic Fluid Injection, 3ml, one time dose. | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal bleed | Gastrointestinal disorders | Systematic Assessment | The patient presented to the emergency department with an upper gastrointestinal bleed. The event was assessed as a serious adverse event that was unexpected and severe in intensity; however, it was determined to be unrelated to the study injection. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Total Knee Arthroplasty | Musculoskeletal and connective tissue disorders | Systematic Assessment | Five participants (1 in the amniotic fluid group and 4 in the corticosteroid group) underwent total knee replacement after enrollment but prior to study completion. All events were determined to be unrelated to the study intervention. |
Protocol deviations and participant eligibility were monitored throughout the study. Procedures were in place to document any errors in treatment administration or deviations from eligibility criteria.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jamie Egbert, MPH | University of Utah Health: Department of Orthopaedics | 801-587-7109 | jamie.egbert@utah.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 23, 2023 | Jan 21, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D010972 | Platelet Activating Factor |
| C116241 | MICU1 protein, human |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D002794 | Choline |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 |
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Half of the patients will be in the SOC treatment arm and half of the patients will be in the AF arm. The PI and patients will be blinded as to the arm in which they will be participating. Once the randomization number is obtained, unblinded research staff will prepare the appropriate study drug. The injections will be blinded to the research coordinator in charge of data entry, the treating physician and the patient.
|
| Standard of Care | Other | Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis |
|
|
Pain was assessed using the Visual Analog Scale for pain (VAS), measured on a scale of 0 to 10. With 0 being no pain at all and 10 being the most pain possible. |
| 6 months |
| Single Assessment Numerical Evaluation (SANE) | Self-reported functional outcomes were evaluated throughout the study period using the Single Assessment Numerical Evaluation (SANE) [scored as a percentage of normal for the affected joint on a scale from 0-100%]. With higher values representing higher levels of function. | 6 months |
| Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT) | Self-reported functional outcomes were evaluated using the PROMIS Physical Function Computer Adaptive Test [self-report of capabilities related to activities of daily living scored from 0 to 100]. With higher values representing higher levels of function. | 6 months |
| 12832377 | Background | Prusa AR, Marton E, Rosner M, Bernaschek G, Hengstschlager M. Oct-4-expressing cells in human amniotic fluid: a new source for stem cell research? Hum Reprod. 2003 Jul;18(7):1489-93. doi: 10.1093/humrep/deg279. |
| 22377907 | Background | Bottai D, Cigognini D, Nicora E, Moro M, Grimoldi MG, Adami R, Abrignani S, Marconi AM, Di Giulio AM, Gorio A. Third trimester amniotic fluid cells with the capacity to develop neural phenotypes and with heterogeneity among sub-populations. Restor Neurol Neurosci. 2012;30(1):55-68. doi: 10.3233/RNN-2011-0620. |
| Background | Johnson, H.L., Peritoneal Immunization. The American Journal of Surgery, 1936. 34(2): p. 266-271 |
| Background | Shimberg, M., The Use of Amniotic Fluid Concentrate in Orthopedic Conditions. The Journal of Bone and Joint Surgery, 1938(20): p. 167-177 |
| 2668811 | Background | Ismail MA, Salti GI, Moawad AH. Effect of amniotic fluid on bacterial recovery and growth: clinical implications. Obstet Gynecol Surv. 1989 Aug;44(8):571-7. doi: 10.1097/00006254-198908000-00001. No abstract available. |
| 2874087 | Background | Ojo VA, Okpere EE, Obaseiki-Ebor EE. Antimicrobial properties of amniotic fluid from some Nigerian women. Int J Gynaecol Obstet. 1986 Apr;24(2):97-101. doi: 10.1016/0020-7292(86)90002-0. |
| 23518680 | Background | Siggers J, Ostergaard MV, Siggers RH, Skovgaard K, Molbak L, Thymann T, Schmidt M, Moller HK, Purup S, Fink LN, Frokiaer H, Boye M, Sangild PT, Bering SB. Postnatal amniotic fluid intake reduces gut inflammatory responses and necrotizing enterocolitis in preterm neonates. Am J Physiol Gastrointest Liver Physiol. 2013 May 15;304(10):G864-75. doi: 10.1152/ajpgi.00278.2012. Epub 2013 Mar 21. |
| 15191823 | Background | Ozgenel GY, Filiz G, Ozcan M. Effects of human amniotic fluid on cartilage regeneration from free perichondrial grafts in rabbits. Br J Plast Surg. 2004 Jul;57(5):423-8. doi: 10.1016/j.bjps.2003.12.021. |
| 15011124 | Background | Ozgenel GY, Filiz G. Combined application of human amniotic membrane wrapping and hyaluronic acid injection in epineurectomized rat sciatic nerve. J Reconstr Microsurg. 2004 Feb;20(2):153-7. doi: 10.1055/s-2004-820772. |
| 15916770 | Background | Karacal N, Kosucu P, Cobanglu U, Kutlu N. Effect of human amniotic fluid on bone healing. J Surg Res. 2005 Dec;129(2):283-7. doi: 10.1016/j.jss.2005.03.026. |
| 18555991 | Background | Castro-Combs J, Noguera G, Cano M, Yew M, Gehlbach PL, Palmer J, Behrens A. Corneal wound healing is modulated by topical application of amniotic fluid in an ex vivo organ culture model. Exp Eye Res. 2008 Jul;87(1):56-63. doi: 10.1016/j.exer.2008.04.010. Epub 2008 Apr 30. |
| 23356944 | Background | Nyman E, Huss F, Nyman T, Junker J, Kratz G. Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: in vitro studies of re-epithelialisation in human skin wounds. J Plast Surg Hand Surg. 2013 Apr;47(2):89-92. doi: 10.3109/2000656X.2012.733169. Epub 2013 Jan 29. |
| 22827842 | Background | Weissenbacher T, Laubender RP, Witkin SS, Gingelmaier A, Schiessl B, Kainer F, Friese K, Jeschke U, Dian D, Karl K. Influence of maternal age, gestational age and fetal gender on expression of immune mediators in amniotic fluid. BMC Res Notes. 2012 Jul 24;5:375. doi: 10.1186/1756-0500-5-375. |
| 6384254 | Background | Merimee TJ, Grant M, Tyson JE. Insulin-like growth factors in amniotic fluid. J Clin Endocrinol Metab. 1984 Oct;59(4):752-5. doi: 10.1210/jcem-59-4-752. |
| 29564213 | Background | Hung M, Bounsanga J, Voss MW, Saltzman CL. Establishing minimum clinically important difference values for the Patient-Reported Outcomes Measurement Information System Physical Function, hip disability and osteoarthritis outcome score for joint reconstruction, and knee injury and osteoarthritis outcome score for joint reconstruction in orthopaedics. World J Orthop. 2018 Mar 18;9(3):41-49. doi: 10.5312/wjo.v9.i3.41. eCollection 2018 Mar 18. |
| 24427427 | Background | Winterstein AP, McGuine TA, Carr KE, Hetzel SJ. Comparison of IKDC and SANE Outcome Measures Following Knee Injury in Active Female Patients. Sports Health. 2013 Nov;5(6):523-9. doi: 10.1177/1941738113499300. |
| 12801417 | Background | Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003 May 25;1:17. doi: 10.1186/1477-7525-1-17. |
| pAF Injection |
For the processed Amniotic Fluid (pAF) injection, the pAF injectate is prepared. The skin is prepped with Chloraprep. The skin is anesthetized using a freezing spray. 3 mLs of the pAF injectable solution is injected into the intra articular space of the knee. Ultrasound guidance will be used for all study injections. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Body Mass Index | Body Mass Index (BMI) was calculated as weight in kilograms divided by height in meters squared (kg/m²). BMI categories were defined according to World Health Organization criteria: Underweight: <18.5 kg/m² Normal weight: 18.5-24.9 kg/m² Overweight: 25.0-29.9 kg/m² Obesity Class I: 30.0-34.9 kg/m² Obesity Class II: 35.0-39.9 kg/m² Obesity Class III: ≥40.0 kg/m² Higher BMI indicates greater body mass and higher obesity classification. | Median | Inter-Quartile Range | kg/m² |
|
| Kellgren-Lawrence Score | Radiographic severity of knee osteoarthritis was graded using the Kellgren-Lawrence (KL) scale (Grade 0-4). Grade 0 = no radiographic features of osteoarthritis Grade 1 = doubtful joint space narrowing and possible osteophytes Grade 2 = definite osteophytes and possible joint space narrowing Grade 3 = multiple osteophytes, definite joint space narrowing, sclerosis, possible bony deformity Grade 4 = large osteophytes, marked joint space narrowing, severe sclerosis, definite bony deformity Higher KL grade indicates more severe osteoarthritis. | Number | Participants |
|
| Visual Analog Scale (VAS) for pain | Pain was assessed using the Visual Analog Scale for pain (VAS), measured on a scale of 0 to 10. With 0 being no pain at all and 10 being the most pain possible. | Median | Inter-Quartile Range | Score on a scale |
|
| Single Assessment Numerical Evaluation (SANE) | Self-reported functional outcomes were evaluated throughout the study period using the Single Assessment Numerical Evaluation (SANE) [scored as a percentage of normal for the affected joint on a scale from 0-100%]. With higher values representing higher levels of function. | Median | Inter-Quartile Range | Percentage score |
|
| Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function CAT | Self-reported functional outcomes were evaluated using the PROMIS Physical Function Computer Adaptive Test [self-report of capabilities related to activities of daily living scored from 0 to 100]. With higher values representing higher levels of function. | Median | Inter-Quartile Range | Scores on a scale |
|
| Knee Injury and Osteoarthritis Outcome Score (KOOS) | Knee Injury and Osteoarthritis Outcome Score (KOOS) [assessment of joint symptoms, pain, and function on a scale from 0 to 100]. With higher scores representing better symptoms, pain and function. | Median | Inter-Quartile Range | Score on a scale |
|
| OG001 | Standard of Care Steroid Injection | Corticosteroids, 3ml, one time dose. |
|
|
| Secondary | Knee Injury and Osteoarthritis Outcome Score (KOOS) | Knee Injury and Osteoarthritis Outcome Score (KOOS) [assessment of joint symptoms, pain, and function on a scale from 0 to 100]. With higher scores representing better symptoms, pain and function. | Three participants did not respond to the 6-month follow-up email within the designated follow-up period and were therefore excluded from the 6-month analysis. | Posted | Median | Inter-Quartile Range | Scores on a scale | 6 months |
|
|
|
| Secondary | Visual Analog Scale for Pain (VAS Pain) | Pain was assessed using the Visual Analog Scale for pain (VAS), measured on a scale of 0 to 10. With 0 being no pain at all and 10 being the most pain possible. | Three participants did not respond to the 6-month follow-up email within the designated follow-up period and were therefore excluded from the 6-month analysis. | Posted | Median | Inter-Quartile Range | Scores on a scale | 6 months |
|
|
|
| Secondary | Single Assessment Numerical Evaluation (SANE) | Self-reported functional outcomes were evaluated throughout the study period using the Single Assessment Numerical Evaluation (SANE) [scored as a percentage of normal for the affected joint on a scale from 0-100%]. With higher values representing higher levels of function. | Three participants did not respond to the 6-month follow-up email within the designated follow-up period and were therefore excluded from the 6-month analysis. | Posted | Median | Inter-Quartile Range | Percentage score | 6 months |
|
|
|
| Secondary | Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT) | Self-reported functional outcomes were evaluated using the PROMIS Physical Function Computer Adaptive Test [self-report of capabilities related to activities of daily living scored from 0 to 100]. With higher values representing higher levels of function. | Three participants did not respond to the 6-month follow-up email within the designated follow-up period and were therefore excluded from the 6-month analysis. | Posted | Median | Inter-Quartile Range | Scores on a scale | 6 months |
|
|
|
| Other Pre-specified | Number of Treatment Emergent Adverse Events (AEs) Directly Related to the Injection. | One adverse event potentially related to the study injection (edema in lower extremity and foot, which resolved) was reported in the Amniotic Fluid treatment group, while no adverse events related to the injection were reported in the corticosteroid treatment group. | Posted | Number | events | 1 day, 2 days, 1 month, 3 months, 6 months, 12 months |
|
|
|
| 30 |
| 1 |
| 30 |
| 1 |
| 30 |
| EG001 | Standard of Care Steroid Injection | Corticosteroids, 3ml, one time dose. | 0 | 30 | 1 | 30 | 4 | 30 |
|
| Myocardial Infarction | Cardiac disorders | Systematic Assessment | The patient presented to the emergency department and was diagnosed with an NSTEMI. The event was assessed as a serious adverse event that was unexpected and life threatening in intensity; however, it was determined to be unrelated to the study. |
|
|
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| Organic Chemicals |
| D000588 | Amines |
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D009861 | Onium Compounds |
| D010742 | Phospholipid Ethers |
| D020404 | Glycerophospholipids |
| D010712 | Phosphatidic Acids |
| D005994 | Glycerophosphates |
| D010743 | Phospholipids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D001779 | Blood Coagulation Factors |
| D001685 | Biological Factors |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
| Sport and Recreation Function subscale |
|