Amniotic Suspension Allograft Injection for Knee Osteoarthritis

Phase 3

Recruiting

• Conditions: Knee; Osteoarthritis
• Interventions: Drug: ASA injection 40 mg group; Drug: ASA injection 20 mg group; Drug: HA injection group; Drug: Normal saline injection group

• Registration Number: NCT06704893
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

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.

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 option1-3. 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 ulcers4. More recently, these tissues have been applied in the orthopedic field5-7. 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 components8. 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 arthritis9,10. Reducing this inflammation can not only alleviate the pain of knee osteoarthritis but also improve the quality of life for patients.

Study Timeline

• Study Start: 2024-10-21
• Study First Submitted: 2024-10-26
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-19
• Last Update Submitted: 2024-11-19
• Study First Posted: 2024-11-26
• Last Update Posted: 2024-11-26
• Primary Completion: 2025-10-01
• Study Completion: 2026-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

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.

8. 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ASA injection 40 mg group	ASA injection 40 mg group	AMNIOGEN® 40mg (HCT Regenerative, New Taipei, Taiwan) was diluted in 3.0 mL of sterile normal saline.
ASA injection 20 mg group	ASA injection 20 mg group	AMNIOGEN® 20mg (HCT Regenerative, New Taipei, Taiwan) was diluted in 3.0 mL of sterile normal saline.
HA injection group	HA injection group	3 ml of HyLink (SEIKAGAKU CORPORATION, Tokyo, Japan)
Normal saline injection group	Normal saline injection group	3 ml of sterile normal saline

Primary Outcome Measures

Name	Time	Method
Visual Analog Scale (VAS)	From enrollment to the end of study at 12 months	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.
Knee Injury and Osteoarthritis Outcome Score (KOOS)	From enrollment to the end of study at 12 months	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).
The World Health Organization Quality of Life Brief Version (WHOQOL-BREF)	From enrollment to the end of study at 12 months	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.

Secondary Outcome Measures

Name	Time	Method
Cartilage Oligomeric Matrix Protein (COMP)	From enrollment to the end of study at 12 months	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.
Number of participants with abnormal Complete Blood Count (CBC)	From enrollment to the end of study at 12 months	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; 1. WBC in 1000/μL; 2. RBC in million/μL; 3. Hemoglobin in g/dL; 4. Hematocrit in %; 5. MCV in fL; 6. MCH in pg/cell; 7. MCHC in g/dL; 8. RDW in %; 9. RDW-SD in fL; 10. Platelet in 1000/μL; 11. PDW in fL; 12. MPV in fL All blood samples will be analyzed at the laboratory of Chang Gung Memorial Hospital. We will count the number of participants with abnormal CBC.
C-reactive protein (CRP)	From enrollment to the end of study at 12 months	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.
Erythrocyte Sedimentation Rate (ESR)	From enrollment to the end of study at 12 months	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.
Cytokine IL-6	From enrollment to the end of study at 12 months	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.
Knee Ultrasound Imaging	From enrollment to the end of study at 12 months	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.
Knee X-ray	From enrollment to the end of study at 12 months	Each participant will undergo knee X-rays (AP view, lateral view, merchant view) at baseline and 12 months post-treatment.

Trial Locations

Locations (2)

Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Kaohsiung Chang Gung Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan