Clinical trial NCT04886960: pAF for the Treatment of Osteoarthritis
Official title: A Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Osteo Arthritis Knee
Keywords: Amniotic Fluid
Osteo Arthritis
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2021-05-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients who are between the ages of 18-70 years
* A confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings consistent with Kellgren-Lawrence Stage 2-3 disease
* Patients who have failed conservative treatment (e.g. steroid, activity modification, therapy, etc.) within 3 months
* Unilateral or bilateral chronic knee joint pain \>4 months
* Patients who are able to ambulate (i.e. not wheelchair bound)
* Patient reported a typical pain of at least 4 out of 10 during the past week using VAS numeric pain scale (0-10)
* Patients who are of childbearing potential must agree to use adequate contraception for 90 days after study drug injection

Exclusion Criteria:

* Subjects who have had a previous injection (i.e. steroid, platelet rich plasma, or other) within the last 3 months
* A focal chondral defect, defined by x-ray evaluation
* BMI \>40 as defined by NIH Clinical Guidelines Body Mass Index
* Concurrent participation in another investigational trial involving systemic administration of agents (within the previous 30 days) or plans to participate in any other allogeneic stem cell therapy trial during the 12 month follow-up period
* Clinical suspicion of infection at injection site
* Any surgeries within 4 weeks, other than diagnostic surgery
* Insulin or self-reported non-insulin dependent diabetic evident of HgA1c ≥8% among known diabetics
* Unable to consent to an English Language Consent Form
* Frank mechanical issues (i.e. locking of the knee)
* Workman's Compensation cases
* Rheumatoid arthritis
* Patients with a known allergy to local anesthetics or components of the study drug (pAF or steroid injection)
* Patients with vascular claudication or neurologic disorders affecting the index lower limb
* Patients with inflammatory arthropathies or connective tissue disorders; or
* Patients with known alcohol or drug abuse or dependence, recreational use of illicit drug or prescription medications, or have used medical marijuana within 7 days of study enrollment
* Patients with history of active cancer/malignancy within 2 years of screening, apart from adequately treated basal cell or squamous cell carcinoma of the skin not associated with the target knee
* Women who are nursing or pregnant
* Patients of childbearing potential who are unwilling to use adequate contraception for 90 days after study drug injection

Primary outcomes:
measure: Repeat allogeneic intra-articular injection within 6 months.
timeFrame: 6 months
Secondary outcomes:
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 6 months
measure: Visual Analog Scale for pain (VAS Pain)
timeFrame: 6 months
measure: Single Assessment Numerical Evaluation (SANE)
timeFrame: 6 months
measure: Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT)
timeFrame: 6 months
Other outcomes:
measure: Number of treatment emergent adverse events (AEs) directly related to the injection.
timeFrame: 1 day, 2 days, 1 month, 3 months, 6 months, 12 months
measure: Knee Injury and Osteoarthritis Outcome Score (KOOS)
timeFrame: 1, 3, 6 and 12 months
measure: Visual Analog Scale for pain (VAS Pain).
timeFrame: 1, 3, 6 and 12 months
measure: Single Assessment Numerical Evaluation (SANE)
timeFrame: 1, 3, 6 and 12 months
measure: Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT)
timeFrame: 1, 3, 6 and 12 months
Locations:
city: Salt Lake City
country: United States
facility: University of Utah Orthopedic Center
state: Utah
Study officials:
affiliation: University of Utah Orthopaedic Center
name: David Petron, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Johnson, H.L., Peritoneal Immunization. The American Journal of Surgery, 1936. 34(2): p. 266-271
citation: Shimberg, M., The Use of Amniotic Fluid Concentrate in Orthopedic Conditions. The Journal of Bone and Joint Surgery, 1938(20): p. 167-177
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.