Amniotic Suspension Allograft Injection for Knee Osteoarthritis (ASAIKO)

The Efficacy of Amniotic Suspension Allograft Injection in the Treatment of Knee Osteoarthritis: a Randomized Double-blind Controlled Trial

There have been few clinical trials on ASA for the treatment of knee osteoarthritis, and there is currently no literature reporting the optimal treatment dosage. Non-surgical treatment options include braces, weight loss, lifestyle changes, oral pain relievers, and intra-articular injections. Recently, placental-derived tissues have gradually been applied in the treatment of knee osteoarthritis. These tissues were initially used primarily for burns, ulcers, and wounds that are difficult to heal, but have now begun to be utilized in the orthopedic field. They have been proven to contain various anti-inflammatory cytokines and growth factors, which can reduce inflammation associated with arthritis. Reducing inflammation not only alleviates the pain of knee osteoarthritis but also improves patients' quality of life. The purpose of this study is to compare the therapeutic effects of amniotic suspension allograft (ASA), hyaluronic acid (HA), and saline on knee osteoarthritis and to examine whether there is a dose-response relationship with ASA injections.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis; Knee
• Intervention / Treatment: Drug: ASA injection 40 mg group; Drug: ASA injection 20 mg group; Drug: HA injection group; Drug: Normal saline injection group

Detailed Description

According to statistics from the Ministry of Health and Welfare, the prevalence of knee osteoarthritis in Taiwan is approximately 15%. The main causes of the disease include overuse of joint cartilage and abnormal synovial fluid secretion, which impair joint mobility and cause symptoms like pain, swelling, and warmth. In severe cases, bone spurs and joint deformities can develop, further limiting mobility. Non-surgical treatment options for knee osteoarthritis currently include the use of braces, weight loss, lifestyle changes, oral pain relievers, and intra-articular injections, with only a small number of patients requiring surgery due to severe joint cartilage wear. In terms of injection treatments, given the limited efficacy of traditional corticosteroid and HA injections for knee osteoarthritis, an increasing number of physicians are using platelet-rich plasma (PRP) injections. Numerous clinical trials have supported this treatment option. However, the effectiveness of PRP treatment is partly dependent on the quality of the patient's blood. If the patient has poor blood quality (e.g., due to old age, multiple chronic diseases, autoimmune disorders, or use of anticoagulants), the efficacy of PRP injections will be significantly reduced.

Recently, a highly promising treatment option-placental-derived tissues-has begun to be used for knee osteoarthritis. Historically, placental-derived tissues have been applied to burns, ulcers, and other difficult-to-heal wounds such as corneal ulcers. More recently, these tissues have been applied in the orthopedic field. These products come in several formulations, some containing pulverized tissues (amniotic membrane, chorion, or both), cells from amniotic fluid, amniotic fluid itself, or a combination of these components. Placental tissues have been shown to contain a variety of anti-inflammatory cytokines, growth factors, and inhibitors, which are believed to reduce the inflammatory response associated with arthritis. Reducing this inflammation can not only alleviate the pain of knee osteoarthritis but also improve the quality of life for patients.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung City, Taiwan, 833
    • Recruiting
    • Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital
    • Contact: Po-Cheng Chen, MD, MPH; Phone Number: 6286 88677317123; Email: b9302081@cgmh.org.tw
    • Principal Investigator: Po-Cheng Chen, MD, MPH
  • Taiwan
    • Kaohsiung, Taiwan, Taiwan, 833
      • Recruiting
      • Kaohsiung Chang Gung Memorial Hospital
      • Contact: Po-Cheng Chen, MD; Phone Number: 88677317123; Email: b9302081@cgmh.org.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 80 years.
2. Body mass index (BMI) less than 40 kg/m².
3. Symptomatic knee osteoarthritis with X-ray evidence graded 2 or 3 on the Kellgren-Lawrence (KL) grading scale.
4. Numerical Rating Scale (NRS) score (scale 1 to 10) for pain greater than 4 over the past 7 days.
5. Able to walk independently or with the aid of a cane.

Exclusion Criteria:

1. Pregnant women or women planning pregnancy.
2. Regular use of anticoagulants.
3. Use of pain medications (except acetaminophen) within 15 days prior to injection.
4. History of substance abuse.
5. Patients who take additional knee symptom-relief medications during the study must report it to the research team; failure to comply will result in exclusion.
6. Corticosteroid or visco-supplementation injection into the affected knee within 3 months prior to enrollment.
7. Knee surgery on the affected side within 12 months before enrollment, or surgery on the contralateral knee within 6 months before enrollment.

9. History of organ or hematopoietic stem cell transplant. 11. Current use of immunosuppressive agents. 12. Diagnosis of cancer within the past 5 years (except for treated basal cell carcinoma).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASA injection 40 mg group; AMNIOGEN® 40mg (HCT Regenerative, New Taipei, Taiwan) was diluted in 3.0 mL of sterile normal saline.	Drug: ASA injection 40 mg group; Participants will receive intra-articular knee injections under ultrasound guidance with AMNIOGEN® 40mg (HCT Regenerative, New Taipei, Taiwan) diluted in 3.0 mL of sterile normal saline.
Experimental: ASA injection 20 mg group; AMNIOGEN® 20mg (HCT Regenerative, New Taipei, Taiwan) was diluted in 3.0 mL of sterile normal saline.	Drug: ASA injection 20 mg group; Participants will receive intra-articular knee injections under ultrasound guidance with AMNIOGEN® 20mg (HCT Regenerative, New Taipei, Taiwan) diluted in 3.0 mL of sterile normal saline.
Active Comparator: HA injection group; 3 ml of HyLink (SEIKAGAKU CORPORATION, Tokyo, Japan)	Drug: HA injection group; Participants will receive intra-articular knee injections under ultrasound guidance with 3 ml of HyLink (SEIKAGAKU CORPORATION, Tokyo, Japan).
Placebo Comparator: Normal saline injection group; 3 ml of sterile normal saline	Drug: Normal saline injection group; Participants will receive intra-articular knee injections under ultrasound guidance with 3 ml of sterile normal saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analog Scale (VAS)	This scale assesses overall pain severity, with scores ranging from 0 (no pain) to 10 (severe pain). Measurements will be taken before treatment and at 1, 3, 6, and 12 months after treatment.	From enrollment to the end of study at 12 months
Knee Injury and Osteoarthritis Outcome Score (KOOS)	This questionnaire measures knee injury and osteoarthritis impact across five domains: pain, symptoms, activities of daily living (ADL), sport and recreation function, and quality of life. Measurements will be collected at baseline and at 1, 3, 6, and 12 months post-treatment. The resulting scores are transformed to a scale from 0 (extreme knee problems) to 100 (no knee problems).	From enrollment to the end of study at 12 months
The World Health Organization Quality of Life Brief Version (WHOQOL-BREF)	This quality-of-life assessment, developed by the World Health Organization, evaluates four domains: physical health, psychological well-being, social relationships, and environment. It will be administered before treatment and at 1, 3, 6, and 12 months post-treatment. The score of each domain ranges from 0 (worst outcome) to 100 (best outcome). The total score is the summation of each domain score.	From enrollment to the end of study at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-reactive protein (CRP)	Each participant will undergo blood test for C-reactive protein (CRP in mg/L) before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital.	From enrollment to the end of study at 12 months
Erythrocyte Sedimentation Rate (ESR)	Each participant will undergo blood test for Erythrocyte Sedimentation Rate (ESR in mm/hr) before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital.	From enrollment to the end of study at 12 months
Cytokine IL-6	Each participant will undergo blood test for cytokine IL-6 in pg/mL before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital.	From enrollment to the end of study at 12 months
Knee Ultrasound Imaging	Each participant will undergo ultrasound evaluation before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. The evaluation will mainly assess the volume of effusion, the degree of damage to the medial and lateral femoral trochlear cartilage17 (grade 0: normal; grade 1: slightly blurred cartilage edges or increased echogenicity of the cartilage; grade 2A: partial thinning of the cartilage, thinning <50% of the original cartilage thickness; grade 2B: partial thinning of the cartilage, thinning >50% of the original cartilage thickness; grade 3: complete loss of cartilage thickness), and whether there is meniscus extrusion in the medial or lateral meniscus.	From enrollment to the end of study at 12 months
Knee X-ray	Each participant will undergo knee X-rays (AP view, lateral view, merchant view) at baseline and 12 months post-treatment.	From enrollment to the end of study at 12 months
Cartilage Oligomeric Matrix Protein (COMP)	Each participant will undergo blood test for Cartilage Oligomeric Matrix Protein (COMP in IU) before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital.	From enrollment to the end of study at 12 months
Number of participants with abnormal Complete Blood Count (CBC)	Each participant will undergo blood tests for Complete Blood Count (CBC) before treatment, and at 1 month, 3 months, 6 months, and 12 months after treatment. Complete Blood Count (CBC) includes; WBC in 1000/μL; RBC in million/μL; Hemoglobin in g/dL; Hematocrit in %; MCV in fL; MCH in pg/cell; MCHC in g/dL; RDW in %; RDW-SD in fL; Platelet in 1000/μL; PDW in fL; MPV in fL All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital. The investigators will count the number of participants with abnormal CBC.	From enrollment to the end of study at 12 months

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 26, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: knee osteoarthritis; double-blind randomized controlled trial; amniotic suspension allograft injection
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Population Characteristics; Demography; Population Groups
• Other Study ID Numbers: 202401278A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Secondary analysis might be performed after the primary study, so IPD will not be shared immediately after finishing the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No