pAF for the Treatment of Osteoarthritis

• ClinicalTrials.gov Identifier: NCT04886960
• Recruitment Status: Recruiting
• First Posted: May 14, 2021
• Last Update Posted: June 15, 2023
• Sponsor: University of Utah
• Information provided by (Responsible Party): David Petron, University of Utah

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Osteo Arthritis Knee	Biological: Amniotic Fluid Injection; Other: Standard of Care	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: 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.
• Primary Purpose: Treatment
• Official Title: A Phase I/II Randomized Double-Blinded Standard of Care (Corticosteroid) vs. Sterile Amniotic Fluid for Osteoarthritis
• Actual Study Start Date: July 8, 2021
• Estimated Primary Completion Date: July 30, 2024
• Estimated Study Completion Date: July 30, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Amniotic Fluid Injection; Amniotic Fluid Injection, 3ml, one time dose.	Biological: Amniotic Fluid Injection; Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis; Other Names: Processed Amniotic Fluid, pAF; Human Amniotic Fluid, hAF
Active Comparator: Standard of Care Steroid Injection; Corticosteroids, 3ml, one time dose.	Other: Standard of Care; Comparison of Standard of Care (Corticosteroid) injection vs. Sterile Processed Amniotic Fluid Injection for Knee Osteoarthritis; Other Name: Corticosteriods 3ml, one time dose

Outcome Measures

Primary Outcome Measures :

1. Repeat allogeneic intra-articular injection within 6 months. [ Time Frame: 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.

Secondary Outcome Measures :

1. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: 6 months ]
   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.
2. Visual Analog Scale for pain (VAS Pain) [ Time Frame: 6 months ]
   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.
3. Single Assessment Numerical Evaluation (SANE) [ Time Frame: 6 months ]
   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.
4. Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT) [ Time Frame: 6 months ]
   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.

Other Outcome Measures:

1. Number of treatment emergent adverse events (AEs) directly related to the injection. [ Time Frame: 1 day, 2 days, 1 month, 3 months, 6 months, 12 months ]
2. Knee Injury and Osteoarthritis Outcome Score (KOOS) [ Time Frame: 1, 3, 6 and 12 months ]
   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.
3. Visual Analog Scale for pain (VAS Pain). [ Time Frame: 1, 3, 6 and 12 months ]
   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.
4. Single Assessment Numerical Evaluation (SANE) [ Time Frame: 1, 3, 6 and 12 months ]
   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.
5. Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function Computer Adaptive Test (PF-CAT) [ Time Frame: 1, 3, 6 and 12 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: David Petron, MD; 801-587-0989; david.petronl@hci.utah.edu

Contact: Jan Pierce, MBA; 801-585-9539; jan.pierce@hsc.utah.edu

Locations

United States, Utah

University of Utah Orthopedic Center; Recruiting

Salt Lake City, Utah, United States, 84108

Contact: David Petron, MD 801-587-0989 david.petronl@hci.utah.edu

Sub-Investigator: Bob Toth, PA, ATC

Sub-Investigator: Nick Monson, DO

Sub-Investigator: John Phillips, PhD

Sub-Investigator: Jan Pierce, MBA

Sub-Investigator: Christopher Gee, MD, MPH

Sub-Investigator: Emily J. Harold, MD

Sub-Investigator: Joy English, MD, RMSK

Sub-Investigator: Daniel Cushman

Sub-Investigator: Amy Powell, MD

Sponsors and Collaborators

University of Utah

Investigators

• Principal Investigator: David Petron, MD; University of Utah Orthopaedic Center

More Information

Additional Information:

Osteoarthritis Fact Sheet. Center for Disease Control and Prevention. 

Publications:

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.

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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.

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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

• Responsible Party: David Petron, Principal Investigator, University of Utah
• ClinicalTrials.gov Identifier: NCT04886960
• Other Study ID Numbers: 128491
• First Posted: May 14, 2021
• Last Update Posted: June 15, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by David Petron, University of Utah:

Amniotic Fluid; Osteo Arthritis

Additional relevant MeSH terms:

Arthritis; Osteoarthritis; Osteoarthritis, Knee; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases