pAF for the Treatment of Osteoarthritis

Osteo Arthritis Knee Clinical Trial

Official title:

A Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04886960
• Other study ID #: 128491
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 8, 2021
• Est. completion date: July 30, 2025

Study information

• Verified date: June 2023
• Source: University of Utah
• Contact: David Petron, MD
• Phone: 801-587-0989
• Email: david.petronl[@]hci.utah.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 30, 2025
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Osteo Arthritis Knee
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Biological:
• Amniotic Fluid Injection
Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis

Other:
• Standard of Care
Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis

Locations

Country	Name	City	State
United States	University of Utah Orthopedic Center	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (19)

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. — View 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. — View 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. — View 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. — View Citation

Johnson, H.L., Peritoneal Immunization. The American Journal of Surgery, 1936. 34(2): p. 266-271

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Shimberg, M., The Use of Amniotic Fluid Concentrate in Orthopedic Conditions. The Journal of Bone and Joint Surgery, 1938(20): p. 167-177

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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of treatment emergent adverse events (AEs) directly related to the injection.		1 day, 2 days, 1 month, 3 months, 6 months, 12 months
Other	Knee Injury and Osteoarthritis Outcome Score (KOOS)	Scale 0-100, where higher numbers indicate less problems. The KOOS is a survey that assesses joint symptoms, pain, pain during daily activities, physical function in daily living, as well as physical function during sports or recreational activities.	1, 3, 6 and 12 months
Other	Visual Analog Scale for pain (VAS Pain).	Scale 0-10, where higher numbers indicate more pain. Pain will be measured by the Visual Analog Scale for pain (VAS Pain). This will consist of a comparison of mean values for VAS scoring scales pre-injection and at the 6 month follow-up assessment. Clinically significant outcomes will be determined based on the minimal clinically important difference (MCID) occurring for each respective scale, which is defined as the smallest reported measurement tool used to quantify perceived level of pain, graded on a scale from 0 to 10 with 0 representing no pain and 10 representing the worse pain possible, and with precise measurement of the marked pain level's distance from 0 comprising the pain level.	1, 3, 6 and 12 months
Other	Single Assessment Numerical Evaluation (SANE)	Scale 0-100, where higher numbers indicate more pain. The SANE asks the patient to evaluate their percentage of normal on the affected joint of region of interest. This is a one-question survey.	1, 3, 6 and 12 months
Other	Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT)	Scale 0-100, where higher numbers indicate better physical functioning, The PF-CAT is a bank of questions related to physical function. It is a computerized adaptive test that asks the patient to self-report capabilities rather than actual performance of physical activities. It includes functioning of upper extremities, lower extremities, and central regions and also assess instrumental activities of daily living, such as running errands.	1, 3, 6 and 12 months
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.	6 months
Secondary	Knee Injury and Osteoarthritis Outcome Score (KOOS)	Scale 0-100, where higher numbers indicate less problems. The KOOS is a survey that assesses joint symptoms, pain, pain during daily activities, physical function in daily living, as well as physical function during sports or recreational activities.	6 months
Secondary	Visual Analog Scale for pain (VAS Pain)	Scale 0-10, where higher numbers indicate more pain. Pain will be measured by the Visual Analog Scale for pain (VAS Pain). This will consist of a comparison of mean values for VAS scoring scales pre-injection and at the 6 month follow-up assessment. Clinically significant outcomes will be determined based on the minimal clinically important difference (MCID) occurring for each respective scale, which is defined as the smallest reported measurement tool used to quantify perceived level of pain, graded on a scale from 0 to 10 with 0 representing no pain and 10 representing the worse pain possible, and with precise measurement of the marked pain level's distance from 0 comprising the pain level.	6 months
Secondary	Single Assessment Numerical Evaluation (SANE)	Scale 0-100, where higher numbers indicate more pain. The SANE asks the patient to evaluate their percentage of normal on the affected joint of region of interest. This is a one-question survey.	6 months
Secondary	Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT)	Scale 0-100, where higher numbers indicate better physical functioning. The PF-CAT is a bank of questions related to physical function. It is a computerized adaptive test that asks the patient to self-report capabilities rather than actual performance of physical activities. It includes functioning of upper extremities, lower extremities, and central regions and also assess instrumental activities of daily living, such as running errands.	6 months

External Links

•   Osteoarthritis Fact Sheet. Center for Disease Control and Prevention.