UMIN-CTR Clinical Trial

Public title

Intraarticular injections of synovial stem cells for osteoarthritis of the knee

Acronym

Intraarticular injections of synovial stem cells for osteoarthritis of the knee

Scientific Title

Intraarticular injections of synovial stem cells for osteoarthritis of the knee

Scientific Title:Acronym

Intraarticular injections of synovial stem cells for osteoarthritis of the knee

Region

Japan

Condition

osteoarthritis

Classification by specialty

Orthopedics

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To investigate the safety and efficacy of intraarticular injections of autologous synovial stem cells into the knee with osteoarthritis.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

1) Safety
Adverse events and treatment-emergent adverse event
2) Efficacy
Change in cartilage area ratio calculated with MRI 3D analysis at 30 weeks after injection of stem cells from baseline

Key secondary outcomes

Efficacy
Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm score, numerical rating scale (NRS), X-ray examination, MRI 3D analysis (meniscal thickness, width, and area ratio)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Maneuver

Other

Interventions/Control_1

Intraarticular injections of synovial stem cells

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1) Patients who are aged 20 years or older on the acquisition date of informed consent before clinical study, and who can give a written informed consent
2) Patients with knee pain
3) Patients diagnosed as osteoarthritis by x-ray examination
4) Patients in whom hyaluronic acid injections were not effective for pain relief
5) Patients in whom exercise therapy in these 3 months have not been effective for pain relief

Key exclusion criteria

1) Patients whose reduction of cartilage area ratio is not greater than 2% from week -30 to week -15
2) Patients who is unidentified
3) Patients who underwent surgery or arthroscopic examination in the affected knee
4) Patients whose clinical symptoms have been sufficiently improved by conservative treatments in the last 3 months
5) Patients with a catching sensation in the knee
6) Patients with knee instability
7) Patients with a history of trauma in the knee
8) Patients for whom MRI is not indicated because of claustrophobia and so on
9) Patients who have had any intraarticular injections (local anesthetic agent, corticosteroid agent, hyaluronic acid) or arthrocentesis in these 3 months
10) Patients with active infection
11) Patients diagnosed or suspected as malignant tumor in these 5 years
12) Patients sensitive to antibiotics (penicillin, streptomycin or amphotericin B)
13) Patients sensitive to animal (bovine) origin materials
14) Patients with poor controlled diabetes
15) Patients with a pacemaker
16) Patients with poor general condition
17) Patients with difficulties in self-determination because of dementia and so on
18) Pregnant women, lactating women and patient who may be pregnant, or patient who desires pregnancy during clinical study
19) Patient who participated in other clinical trials, patient participating in other clinical studies and patient planning to participate in other clinical studies while participating in this clinical study within 12 weeks before the start of transplantation of cellular product
20) Patients for whom doctors decide as not appropriate to participate in the clinical study

Target sample size

10

Name of lead principal investigator

1st name	Ichiro
Middle name
Last name	Sekiya

Organization

Tokyo Medical and Dental University

Division name

Center for Stem Cell and Regenerative Medicine

Zip code

113-8510

Address

1-5-45 Yushima, Bunkyo-ku, Tokyo

TEL

03-5803-4017

Email

sekiya.arm@tmd.ac.jp

Name of contact person

1st name	Office
Middle name
Last name	Administrator

Organization

Medical Hospital of Tokyo Medical and Dental University

Division name

Clinical Research Center

Zip code

113-8510

Address

1-5-45 Yushima, Bunkyo-ku, Tokyo

TEL

03-5803-5612

Homepage URL

http://www.tmd.ac.jp/medhospital/topics/

Email

tiken.crc@tmd.ac.jp

Institute

Medical Hospital of Tokyo Medical and Dental University

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Tokyo Medical and Dental University Hospital of Medicine, Institutional Review Board

Address

1-5-45, Yushima, Bunkyo-ku, Tokyo

Tel

03-5803-5612

Email

tiken.crc@tmd.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

06

Month

01

Day

URL releasing protocol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257723/

Publication of results

Published

URL related to results and publications

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257723/

Number of participants that the trial has enrolled

14

Results

Fully automatic 3D MRI analysis showed that synovial MSC injections suppressed cartilage loss in the knees of patients with progressive OA.

Results date posted

2023

Year

04

Month

02

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The eight patients included five females and three males ranging in age from 51 to 79 years and BMI from 23 to 30. The KL radiographic OA grade was grade 2 for 4 knees, grade 3 for 3 knees, and grade 4 for 1 knee. All patients showed medial OA.

Participant flow

Fourteen patients were initially enrolled in this clinical study, but five were excluded because they showed no detectable cartilage loss. Nine patients underwent synovium harvesting, but one patient was withdrawn from the study because the cells had a suspected bacterial contamination (although this bacterial infection was eventually refuted). Eight patients therefore completed the study.

Adverse events

A total of 8 mild adverse events were recorded among the 8 patients. MSC injection could not be ruled out as the cause of two adverse events. Patient 02 reported knee pain for 1 week just after the first injection. Patient 01 reported itching in both hands that occurred 1 week after the first injection and lasted for one week. Adverse events considered not associated with MSC injection were thigh pain, nausea, vomiting, and rash before the injections and contralateral knee pain and shoulder cuff tear after the injections.

Outcome measures

Eight OA patients underwent MSC injections. The projected cartilage area ratio significantly decreased by 0.07 in the 30 weeks before MSC injections (p = 0.01), but no further decreases occurred in the 30 weeks after MSC injections. The projected cartilage area ratio at the femoral posteromedial region showed a significant difference between 30 weeks before and 30 weeks after MSC injections. The Lysholm Knee Score, KOOS, and NRS values improved significantly after the injections.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

08

Month

01

Day

Date of IRB

2017

Year

03

Month

16

Day

Anticipated trial start date

2017

Year

12

Month

26

Day

Last follow-up date

2020

Year

03

Month

10

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

03

Month

28

Day

Last modified on

2023

Year

04

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000029967