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MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS)

Primary Purpose

Multiple Sclerosis

Status

Unknown status

Phase

Phase 1

Locations

Italy

Study Type

Interventional

Intervention

Autologous Mesenchymal Stem Cells

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, Mesenchymal stem cells

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- 1. Diagnosis of MS

a. Relapsing remitting MS (RRMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by one or more of the following: i. ≥1 clinically documented relapse in past 12 months

ii. ≥2 clinically documented relapses in last 24 months

iii. ≥1 GEL at MRI performed within the last 12 months

b. Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both:

i. an increase of ≥1 point of the expanded disability status scale (EDSS) (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥ 5.5) in the last 12 months

ii. ≥1 clinically documented relapse or ≥ 1 GEL at MRI within the last twelve months.

c. Primary progressive MS (PPMS) patients with all the following features:

i. an increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥5.5), in the last twelve months

ii. ≥ 1 GEL at MRI performed within the last 12 months

iii. positive cerebrospinal fluid (CSF) (oligoclonal banding

2. Age 18 to 50 years
3. Disease duration 2 to 10 years (included)
4. EDSS 3.0 to 6.5

Exclusion Criteria:

1. RRMS not fulfilling inclusion criteria
2. SPMS not fulfilling inclusion criteria
3. PPMS not fulfilling inclusion criteria
4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C
5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization
6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization
7. Treatment with corticosteroids within the 30 days prior to randomization
8. Relapse occurred during the 60 days prior to randomization
9. Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
10. Severely limited life expectancy by another co-morbid illness
11. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts
12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study)
13. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination.
14. Inability to give written informed consent in accordance with research ethics board guidelines

Sites / Locations

University of GenovaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Autologous Mesenchymal Stem Cells

Suspension media

Arm Description

At week 0 a single infusion of either ex-vivo expanded autologous MSC or suspension media will be administered intravenously at a dose of 1-2 x 1000000 MSC/Kg body weight. At week 24, another infusion will be performed for cross-over re-treatment: at week 24 treatments will be reversed compared to week 0

Outcomes

Primary Outcome Measures

Safety

Incidence and severity of adverse events in MSC treatment group compared to placebo group.

efficacy

total number of contrast-enhancing lesions (GEL) at MRI scan

Secondary Outcome Measures

Efficacy

Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.

Efficacy

Combined unique MRI activity (number of new or enlarging T2, or enhancing or re-enhancing lesions), volume of GEL and volume of black holes (BH) over 4, 12, 24 weeks compared between treatment groups.

Efficacy

Combined unique MRI activity, volume of GEL and volume of BH over week 28, 36 and 48 compared with the same outcomes over 4, 12 and 24 weeks.

Efficacy

Number of relapses in MSC treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups.

Efficacy

Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over

Full Information

NCT ID

NCT01854957

First Posted

May 8, 2013

Last Updated

May 13, 2013

Sponsor

Antonio Uccelli

Collaborators

Azienda Ospedaliera Universitaria Integrata Verona, Ospedale San Raffaele

1. Study Identification

Unique Protocol Identification Number

NCT01854957

Brief Title

MEsenchymal StEm Cells for Multiple Sclerosis

Acronym

MESEMS

Official Title

MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS) Phase I-II Clinical Trial With Autologous Mesenchymal Stem Cells (MSCs) for the Therapy of Multiple Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

May 2013

Overall Recruitment Status

Unknown status

Study Start Date

July 2012 (undefined)

Primary Completion Date

July 2014 (Anticipated)

Study Completion Date

September 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Antonio Uccelli

Collaborators

Azienda Ospedaliera Universitaria Integrata Verona, Ospedale San Raffaele

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

A double-blind, randomized, cross-over phase I/II study to evaluate the safety and the efficacy of the intravenous administration of autologous Mesenchymal Stem Cells (MSC) to patients with active multiple sclerosis (MS) resistant to currently available therapies.

Detailed Description

The mechanism of action of MSC relies on their ability to modulate pathogenic immune responses and provide neuroprotection through the release of anti-apoptotic, anti-oxidant and trophic factors as demonstrated by in vitro and in vivo preclinical studies. Patients will be randomized to receive immediate vs. delayed treatment with either a dose equal to 1-2 millions/kg of body weight of autologous MSC, or equivalent volume of suspension media at baseline. At 6 months treatments will be reversed. The primary outcome of this study is to evaluate treatment's safety within one year from MSC administration by measuring the the number, time-frame and severity of adverse event and treatment's activity in terms of reduction in the total number of contrast-gadolinium enhancing lesions (GEL) by magnetic resonance imaging (MRI) scans. Secondary outcomes are to gain preliminary information on the efficacy of the experimental treatment in terms of combined MRI activity and clinical efficacy (incidence of relapses and disability progression).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Multiple sclerosis, Mesenchymal stem cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Autologous Mesenchymal Stem Cells

Arm Type

Experimental

Arm Description

Arm Title

Suspension media

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Autologous Mesenchymal Stem Cells

Intervention Description

Single dose of 1-2 x 1000000 cells/Kg body weight

Primary Outcome Measure Information:

Title

Safety

Description

Incidence and severity of adverse events in MSC treatment group compared to placebo group.

Time Frame

24 weeks from the first infusion

Title

efficacy

Description

total number of contrast-enhancing lesions (GEL) at MRI scan

Time Frame

24 weeks from the first infusion

Secondary Outcome Measure Information:

Title

Efficacy

Description

Number of GEL counted over week 28, 36 and 48 compared with the number of GEL counted over 4, 12 and 24 weeks.

Time Frame

48 weeks from the first infusion

Title

Efficacy

Description

Time Frame

24 weeks form the first infusion

Title

Efficacy

Description

Combined unique MRI activity, volume of GEL and volume of BH over week 28, 36 and 48 compared with the same outcomes over 4, 12 and 24 weeks.

Time Frame

48 weeks from the first infusion

Title

Efficacy

Description

Number of relapses in MSC treatment group vs. placebo group in the first 24 weeks and after cross-over re-treatment in the two groups.

Time Frame

48 weeks from the first infusion

Title

Efficacy

Description

Time to sustained progression of disability and proportion of progression-free patients compared between treatment groups during the first 24 weeks and after cross-over

Time Frame

48 weeks from the first infusion

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - 1. Diagnosis of MS a. Relapsing remitting MS (RRMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by one or more of the following: i. ≥1 clinically documented relapse in past 12 months ii. ≥2 clinically documented relapses in last 24 months iii. ≥1 GEL at MRI performed within the last 12 months b. Secondary progressive MS (SPMS) not responding to at least a year of attempted therapy with one or more of the approved therapies (beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, fingolimod) as evidenced by both: i. an increase of ≥1 point of the expanded disability status scale (EDSS) (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥ 5.5) in the last 12 months ii. ≥1 clinically documented relapse or ≥ 1 GEL at MRI within the last twelve months. c. Primary progressive MS (PPMS) patients with all the following features: i. an increase of ≥1 EDSS point (if at randomization EDSS ≤ 5.0) or 0.5 EDSS point (if at randomization EDSS ≥5.5), in the last twelve months ii. ≥ 1 GEL at MRI performed within the last 12 months iii. positive cerebrospinal fluid (CSF) (oligoclonal banding 2. Age 18 to 50 years 3. Disease duration 2 to 10 years (included) 4. EDSS 3.0 to 6.5 Exclusion Criteria: 1. RRMS not fulfilling inclusion criteria 2. SPMS not fulfilling inclusion criteria 3. PPMS not fulfilling inclusion criteria 4. Any active or chronic infection including infection with HIV1-2 or chronic Hepatitis B or Hepatitis C 5. Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the 3 months prior to randomization 6. Treatment with interferon-beta or glatiramer acetate within the 30 days prior to randomization 7. Treatment with corticosteroids within the 30 days prior to randomization 8. Relapse occurred during the 60 days prior to randomization 9. Previous history of a malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year 10. Severely limited life expectancy by another co-morbid illness 11. History of previous diagnosis of myelodysplasia or previous hematologic disease or current clinically relevant abnormalities of white blood cell counts 12. Pregnancy or risk or pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study) 13. eGFR < 60 mL/min/1.73m2 or known renal failure or inability to undergo MRI examination. 14. Inability to give written informed consent in accordance with research ethics board guidelines

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Antonio Uccelli, MD

Phone

+390103537028

MESEMS@unige.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giancarlo Comi, MD

Organizational Affiliation

Ospedale San Raffaele

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Bruno Bonetti, MD

Organizational Affiliation

Azienda Ospedaliera Universitaria Integrata di Verona

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Genova

City

Genova

ZIP/Postal Code

16132

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Antonio Uccelli, MD, PhD

12. IPD Sharing Statement

Citations:

PubMed Identifier

35078125

Citation

Thebault S, Reaume M, Marrie RA, Marriott JJ, Furlan R, Laroni A, Booth RA, Uccelli A, Freedman MS. High or increasing serum NfL is predictive of impending multiple sclerosis relapses. Mult Scler Relat Disord. 2022 Mar;59:103535. doi: 10.1016/j.msard.2022.103535. Epub 2022 Jan 19.

Results Reference

derived

PubMed Identifier

31072380

Citation

Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, Muraro PA, Oliveri RS, Radue EW, Sellner J, Soelberg Sorensen P, Sormani MP, Wuerfel JT, Battaglia MA, Freedman MS; MESEMS study group. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019 May 9;20(1):263. doi: 10.1186/s13063-019-3346-z.

Results Reference

derived

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MEsenchymal StEm Cells for Multiple Sclerosis

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