Allogenic Mesenchymal Stem Cell Intraarticular Injection for Knee Osteoarthritis Therapy (STEMJOINT)

Allogenic Mesenchymal Stem Cell Intraarticular Injection for Knee Osteoarthritis Therapy, an RCT Explorative Mode-of-action Study

This phase I and II double blinded randomized clinical controlled trial investigates the safety and efficacy of intraarticular knee injection with allogenic adipose derived mesenchymal stem cells (AD-MSC), in patients suffering from mild-moderate knee osteoarthritis compared to placebo injection with saline.

Study Overview

• Status: Recruiting
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Allogenic adipose derived mesenchymal stem cells (AD-MSC); Other: Saline

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rasmus Aabling, MD; Phone Number: +4528496767; Email: rasaab@clin.au.dk
• Study Contact Backup: Name: Michael Pedersen, Professor; Email: michael@clin.au.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Aarhus University
    • Contact: Rasmus Aabling, MD; Phone Number: +45 78450000; Email: rasaab@clin.au.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Chronic knee pain (defined for at least 6 months with NRS 4 or above when pain worst)
• Patients with Grade II-III osteoarthritis according to the Kellgren Lawrence Classification and a joint width space of 1-3 mm.
• Axial hip, knee, ankle x-ray with no more than 5 degrees valgus/varus deformity
• Medial, lateral or dual compartment OA as determined above
• BMI <35
• Danish speaker
• Patients must be legally competent and must be able to sign the written consent

Exclusion Criteria:

• Severe Osteoarthritis (Grade IV according to Kellgren Lavrence Classification)
• Intraarticular tumor, infection or fracture
• Pregnancy and breast feeding
• Cognitive impairment
• Treatment with cytostatic drugs
• Previous intraarticular knee injection in the past 3 mo.
• Unable to perform MRI scan (non-compatible implants, claustrophobia and severe obesity(>BMI 35)
• Previous ligament reconstruction
• Meniscal operation with resection with more than 50% or multiple meniscal operations (more than one resection)
• Diabetes mellitus type 1 and 2
• Knee instability on physical examination
• History of allergy to antibiotics
• Concomitant severe infection, malignant tumor, coagulation diseases or uncontrolled or unmanaged systemic disease
• Presence of other types of inflammatory arthritis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Single intraarticular knee injection with allogenic adipose derived mesenchymal stem cells (AD-MSC) 20 million AD-MSC in 10 mL saline	Biological: Allogenic adipose derived mesenchymal stem cells (AD-MSC); Laboratory isolated, cultivated and cryopreserved allogenic adipose derived mesenchymal stem cells (AD-MSC) from health donors undergoing cometic plastic surgery will be thawed on the injection day and formulated in 10 mL saline. The AD-MSCs will then be intraarticular injected using ultrasonic guidance.
Placebo Comparator: Control; Single intraarticular knee injection with saline alone 10 mL saline	Other: Saline; 10 mL saline will be intraarticular injected using ultrasonic guidance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observation (change) of adverse events	Pain Diary first 30 days after treatment, any reported adverse events after treatment	Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years
Change in Knee symptoms (questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS) (symptoms)) from baseline	(questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS) (symptoms))	Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain from baseline	Numeric Rating Scale (NRS)	Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years
Observation (change) of cartilage regeneration compared to baseline	MRI Osteoarthritis Knee Score	Baseline, 3 months, 12 months, 24 months
Observation (change) of quantitative cartilage regeneration compared to baseline	Quantitative MRI (unit: stress and strain and volumen cartilage)	Baseline, 3 months, 12 months, 24 months
Improvement (change) during clinical examination with range of motion compared to baseline	Range of motion (unit: degrees)	Baseline, 3 months, 12 months, 24 months
Improvement (change) during clinical examination with Effusion tests (swelling) compared to baseline	Effusion tests (swelling) (unit: effusion (YES/NO))	Baseline, 3 months, 12 months, 24 months
Improvement (change) during clinical examination with measurement of knee diameter (swelling) compared to baseline	Measure knee diameter (unit: cm)	Baseline, 3 months, 12 months, 24 months
Improvement (change) during clinical examination with measurement of quadriceps muscle diameter (atrofi) compared to baseline	Measure quadriceps muscle (unit: cm)	Baseline, 3 months, 12 months, 24 months

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Investigators: Principal Investigator: Rasmus Aabling, MD, University of Aarhus

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: June 5, 2023
• First Submitted That Met QC Criteria: June 26, 2023
• First Posted (Actual): July 6, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2024
• Last Update Submitted That Met QC Criteria: June 8, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: stem cells; mesenchymal stem cells; adipose derived mesenchymal stem cells; allogenic adipose derived mesenchymal stem cells
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: STEMJOINT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No