AzTrials
AzTrials

OsteoarthritisPhase 1/2NCT02123368

Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells

A Phase 1/2 study testing Hyaluronic acid, 10 million Bone marrow mesenchimal stem cells and 100 million Bone marrow mesenchimal stem cells in people with Osteoarthritis, run by Clinica Universidad de Navarra, Universidad de Navarra at 2 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) in patients with knee osteoarthritis. Read more about this study

Who is it for?
Ages 50 to 80 years
Conditions the study is for
Osteoarthritis
What is being tested?
Hyaluronic acid, 10 million Bone marrow mesenchimal stem cells and 100 million Bone marrow mesenchimal stem cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesSpain
Study dates
May 2012to Feb 2015
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males and females between 50 and 80 year old.
  • Diagnosis of knee OA according to the criteria of osteoarthritis of the ACR (American College of Rheumatology).
  • Joint pain equal or greater than 2.5 points on the visual analogue scale (VAS).
  • Radiological Classification: Kellgren-Lawrence scale greater or equal to 2.
  • Body mass index between 20 and 35 kg/m2.
  • Ability to follow during the study period.

Who cannot join

  • Bilateral Osteoarthritis of the Knee requiring treatment in both knees.
  • Previous diagnosis of polyarticular disease.
  • Severe mechanical deformation.
  • Arthroscopy during the previous 6 months.
  • Intraarticular infiltration of hyaluronic acid in the last 6 months.
  • Systemic autoimmune rheumatic disease.
Show all 13Show fewer
  • Poorly controlled diabetes mellitus.
  • Blood dyscrasias.
  • Immunosuppressive or anticoagulant treatments.
  • Treatment with corticosteroids in the 3 months prior to inclusion in the study.
  • NSAID therapy within 15 days prior to inclusion in the study.
  • Patients with a history of allergy to penicillin or streptomycin.
  • Allergy to hyaluronic acid or poultry proteins.

Trial locations and contacts

2 sites in 1 country.

Spain2 sites
  • Orthopaedic and traumatology department. Clínica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Traumatology department. Complejo Hospitalario de Salamanca

    Salamanca, Castille and León, 37007

Other trials in Spain

About this study

Official title: Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells

Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) in patients with knee osteoarthritis.

Patients and methods

Read more

Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

  1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.
  2. Group B: Low Dosage of MSCs . Intra-articular injection of 10 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid ( Hyalone®).
  3. Group C : High dose of MSCs. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo ( cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid (Hyalone®).

The primary endpoint is safety and feasibility. The investigators registered the occurrence of complications and / or adverse effects during the study.

In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters:

  • Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS.
  • Radiographic (baseline, 6 and 12 months since treatment): Femorotibial space.
  • Radiographic using MRI (baseline, 6 and 12 months since treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.
Read the detailed description

Purpose: To determine the safety, feasibility and effectiveness (clinical and radiological) of intra-articular administration of autologous mesenchymal stem cells (MSCs) in patients with knee osteoarthritis.

Patients and methods

Clinical trial phase I- II, randomized , multicenter , with three treatment arms and 10 patients for each group. The investigators compare the intraarticular injection of hialuronic acid against the administration of two different doses of mesenchymal stem cells with hialuronic acid according to the following scheme:

  1. Group A: intra-articular injection of hyaluronic acid (Hyalone®). Single dose.
  2. Group B: Low Dosage of MSCs . Intra-articular injection of 10 million autologous mesenchymal progenitor stem cells cultured ex - vivo (cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid ( Hyalone®).
  3. Group C : High dose of MSCs. Intra-articular injection of 100 million autologous mesenchymal progenitor stem cells cultured ex - vivo ( cell suspension sterile small volume (5-10 ml ) in a vehicle suitable for intraarticular injection ) followed by an intraarticular injection Hiaurónico Acid (Hyalone®).

The autologous mesenchymal stem cells are obtained from the iliac crest and cultured ex vivo under local anesthesia and sedation.

The primary endpoint is safety and feasibility. The investigators registered the occurrence of complications and / or adverse effects during the study.

In addition the investigators assess the response to intra-articular infusion of CMM analyzing the following parameters:

  • Clinical assessment of pain and function (Baseline, 1, 3, 6 and 12 months since treatment): VAS , WOMAC , KOOS , EuroQol, SF-16, Lequesne , WOMAC , KOOS.
  • Radiographic (baseline, 6 and 12 months since treatment): Femorotibial space.
  • Radiographic using MRI (baseline, 6 and 12 months since treatment): by assessing the number location of the lesions , cartilage thickness , signal intensity , subchondral bone alteration , volume and WORMS and dGEMRIC protocols.

All patients met the following inclusion and exclusion criteria:

Inclusion Criteria:

  • Males and females between 50 and 80 year old.
  • Diagnosis of knee OA according to the criteria of osteoarthritis of the ACR (American College of Rheumatology).
  • Joint pain equal or greater than 2.5 points on the visual analogue scale (VAS).
  • Radiological Classification: Kellgren-Lawrence scale greater or equal to 2.
  • Body mass index between 20 and 35 kg/m2.
  • Ability to follow during the study period.

Exclusion Criteria:

  • Bilateral Osteoarthritis of the Knee requiring treatment in both knees.
  • Previous diagnosis of polyarticular disease.
  • Severe mechanical deformation.
  • Arthroscopy during the previous 6 months.
  • Intraarticular infiltration of hyaluronic acid in the last 6 months.
  • Systemic autoimmune rheumatic disease.
  • Poorly controlled diabetes mellitus.
  • Blood dyscrasias.
  • Immunosuppressive or anticoagulant treatments.
  • Treatment with corticosteroids in the 3 months prior to inclusion in the study.
  • NSAID therapy within 15 days prior to inclusion in the study.
  • Patients with a history of allergy to penicillin or streptomycin.
  • Allergy to hyaluronic acid or poultry proteins.
Conditions
Osteoarthritis
Being tested
Hyaluronic acid, 10 million Bone marrow mesenchimal stem cells, 100 million Bone marrow mesenchimal stem cells
Keywords
Osteoarthritis, Mesenchimal stem cell, Knee
Medical subject headings
Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hyaluronic acidDrug

    Also called HyalOne

    Single intraarticular injection of Hyaluronic acid (Hyal One)

  • 10 million Bone marrow mesenchimal stem cellsBiological

    10 million of Bone marrow mesenchimal stem cells

  • 100 million Bone marrow mesenchimal stem cellsBiological

    100 million of Bone marrow mesenchimal stem cells

Study groups in NCT02123368
Study groupRoleWhat they receive
Hialuronic acidActive comparatorSingle intraarticular injection of Hyaluronic acid (Hyal One)
Receives: Drug: Hyaluronic acid
Hyaluronic acid and MSC 10Active comparatorSingle intraarticular injection of Hyaluronic acid (Hyal One) 10 million Bone marrow mesenchimal stem cells
Receives: Drug: Hyaluronic acid; Biological: 10 million Bone marrow mesenchimal stem cells
Hyaluronic acid AND MSC 100Active comparatorSingle intraarticular injection of Hyaluronic acid (Hyal One) 100 million Bone marrow mesenchimal stem cells
Receives: Drug: Hyaluronic acid; Biological: 100 million Bone marrow mesenchimal stem cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Baseline Visual analogue scale (VAS)

    Baseline Visual analogue scale (VAS)

    Measured: prior to the initial dose on day 1

  2. Baseline value of knee injury and osteoarthritis outcome score (Koos).

    Prior to the intervention on day 1 value of knee injury and osteoarthritis outcome score (Koos).

    Measured: Prior to the intervention on day 1

  3. Baseline Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).

    Prior to the intervention on day 1 Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC).

    Measured: Prior to the intervention on day 1

  4. Baseline SF-36 value

    Prior to the intervention on day 1 SF-36 value

    Measured: Prior to the intervention on day 1

  5. Baseline euroquol 5D value

    Pretreatment euroquol 5D value

    Measured: Prior to the intervention on day 1

  6. Baseline Lequesne index

    Prior to the intervention on day 1 Lequesne index

    Measured: Prior to the intervention on day 1

  7. Baseline femorotibial distance

    Prior to the intervention femoritibial distance on rosenberg x-ray view

    Measured: Prior to the intervention

  8. Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events Number of Participants with Serious and Non-Serious Adverse Events

    During the follow up

    Measured: Follow up

  9. Visual analogue scale (VAS) at on month

    Visual analogue scale (VAS) at on month

    Measured: 1 month

  10. Visual analogue scale (VAS) at 3 months

    Visual analogue scale (VAS) at 3 months

    Measured: 3 months

  11. Visual analogue scale (VAS) at 6 months

    Visual analogue scale (VAS) at 6 months

    Measured: 6 months

  12. Visual analogue scale (VAS) at 12 months

    Visual analogue scale (VAS) at 12 months

    Measured: 12 months

  13. Value of knee injury and osteoarthritis outcome score (Koos) at 1 month

    Value of knee injury and osteoarthritis outcome score (Koos) at 1 month

    Measured: 1 month

  14. Value of knee injury and osteoarthritis outcome score (Koos) at 3 month

    Value of knee injury and osteoarthritis outcome score (Koos) at 3 month

    Measured: 3 Months

  15. Value of knee injury and osteoarthritis outcome score (Koos) at 6 month

    Value of knee injury and osteoarthritis outcome score (Koos) at 6 month

    Measured: 6 months

  16. Value of knee injury and osteoarthritis outcome score (Koos) at 12 months

    Value of knee injury and osteoarthritis outcome score (Koos) at 12 months

    Measured: 12 months

  17. Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month

    Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month

    Measured: 1 month

  18. Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 3 month

    Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 1 month

    Measured: 3 months

  19. Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month

    Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 6 month

    Measured: 6 months

  20. Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months

    Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) at 12 months

    Measured: 12 months

  21. SF-36 value at 1 month

    SF-36 value

    Measured: 1 month

  22. SF 36 value at 3 months

    SF 36 value at 3 months

    Measured: 3 months

  23. SF 36 value at 6 months

    SF 36 value at 6 months

    Measured: 6 months

  24. SF 36 value at 12 months

    SF 36 value at 12 months

    Measured: 12 months

  25. Euroquol 5D value at 1 month

    Euroquol 5D value at 1 month

    Measured: 1 MOnth

  26. Euroquol 5D value at 3 months

    Euroquol 5D value at 3 months

    Measured: 3 months

  27. Euroquol 5D value at 6 months

    Euroquol 5D value at 6 months

    Measured: 6 months

  28. Euroquol 5D value at 12 months

    Euroquol 5D value at 12 months

    Measured: 12 months

  29. Lequesne index at 1 month

    Lequesne index at 1 month

    Measured: 1 month

  30. Lequesne index at 3 months

    Lequesne index at 3 months

    Measured: 3 months

  31. Lequesne index at 6 months

    Lequesne index at 6 months

    Measured: 6 months

  32. Lequesne index at 12 months

    Lequesne index at 12 months

    Measured: 12 months

  33. Femorotibial distance at 6 months

    Femorotibial distance at 6 months

    Measured: 6 months

  34. Femorotibial distance at 12 months

    Femorotibial distance at 12 months

    Measured: 12 months

  35. Baseline MRI WORMS protocol

    Prior to the intervention MRI WORMS protocol

    Measured: Prior to the intervention

  36. MRI WORMS protocol score at 6 months

    MRI WORMS protocol score at 6 months

    Measured: 6 months

  37. MRI WORMS protocol score at 12 months

    MRI WORMS protocol score at 12 months

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Apr 2014 (estimated)
  2. Study startMay 2012
  3. Primary completionNov 2014
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02123368
Sponsor's protocol ID
CMM/ART
Other IDs
2009-017624-72, 2009
Status last verified
Oct 2017
First submitted
12 Nov 2013
Last updated
24 Oct 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Lamo-Espinosa JM, Prosper F, Blanco JF, Sanchez-Guijo F, Alberca M, Garcia V, Gonzalez-Vallinas M, Garcia-Sancho J. Long-term efficacy of autologous bone marrow mesenchymal stromal cells for treatment of knee osteoarthritis. J Transl Med. 2021 Dec 11;19(1):506. doi: 10.1186/s12967-021-03160-2.

    PubMed 34895259
  • Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Lopez-Elio S, Andreu E, Sanchez-Guijo F, Aquerreta JD, Bondia JM, Valenti-Azcarate A, Del Consuelo Del Canizo M, Villaron EM, Valenti-Nin JR, Prosper F. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2018 Jul 31;16(1):213. doi: 10.1186/s12967-018-1591-7.

    PubMed 30064455
  • Lamo-Espinosa JM, Mora G, Blanco JF, Granero-Molto F, Nunez-Cordoba JM, Sanchez-Echenique C, Bondia JM, Aquerreta JD, Andreu EJ, Ornilla E, Villaron EM, Valenti-Azcarate A, Sanchez-Guijo F, Del Canizo MC, Valenti-Nin JR, Prosper F. Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J Transl Med. 2016 Aug 26;14(1):246. doi: 10.1186/s12967-016-0998-2.

    PubMed 27565858

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Hyaluronic acid, 10 million Bone marrow mesenchimal stem cells and 100 million Bone marrow mesenchimal stem cells in people with Osteoarthritis, run by Clinica Universidad de Navarra, Universidad de Navarra at 2 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Baseline Visual analogue scale (VAS) (time frame: prior to the initial dose on day 1). The study lists 37 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02123368, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2017.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in