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Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis (SMART-MS)

Primary Purpose

Multiple Sclerosis, Progressive Multiple Sclerosis

Status
Active
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
MSCs
Saline
Sponsored by
Haukeland University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥18 to ≤55, both genders
  2. Diagnosis of secondary progressive or primary progressive MS using revised McDonald criteria of clinically definite MS
  3. An EDSS score of 4 to 7
  4. Disease duration 2 - 15 years
  5. Signed, written informed consent

Exclusion Criteria:

  1. Any illness or prior/ongoing treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate autologous stem cell treatment
  2. Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity
  3. Current immunomodulatory/immunosuppressive treatment
  4. Immunomodulatory/immunosuppressive treatment within 6 months prior to inclusion. This includes, but is not restricted to treatment with natalizumab, fingolimod, dimetylfumurat, glatiramer acetate, interferon beta medications, teriflunomide, and siponimod.
  5. Treatment with kladribin, ocrelizumab, rituximab, and alemtuzumab within 12 months prior to inclusion
  6. Treatment with hematopoietic stem cell therapy within 12 months prior to inclusion
  7. Treatment with glucocorticoids or ACTH within three months prior to start of inclusion
  8. Having experienced an MS relapse within 2 years prior to study inclusion
  9. Current treatment with fampridin
  10. History of malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year
  11. Severely limited life expectancy by another co-morbid illness
  12. History of previous diagnosis of myelodysplasia or previous hematologic disease (including lymphoproliferative disease, bone marrow insufficiency or previous lymphoid irradiation) or current clinically relevant abnormalities of white blood cell counts
  13. Immunocompromised patients
  14. Estimated glomerular filtration rate <60 ml/min/1.73 m2 or known renal failure
  15. Bleeding or clotting diathesis or the use of antithrombotic or anticoagulative treatment
  16. Platelet (thrombocyte) count <100 x 10*9/L
  17. Participation in another experimental clinical study within the preceding 12 months
  18. Contraindications to MRI
  19. Prior or current major depression
  20. Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.
  21. Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study), breastfeeding or lactation
  22. History of autologous/allogenic bone marrow transplantation or peripheral blood cell transplant
  23. Known hypersensitivity against paracetamol, codein or xylocain
  24. Diagnosis or strong suspicion of polyneuropathy
  25. Prior or current alcohol or drug dependencies
  26. Inability to give informed consent

Sites / Locations

  • University hospital of North Norway
  • St.Olav university hospital
  • Haukeland University Hospital
  • Akershus university hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm A - Crossover with MSCs at baseline and placebo at 6 months

Arm B - Crossover with placebo at baseline and MSCs at 6 months

Arm Description

Receives mesenchymal stem cells at baseline and placebo at 6 months

Receives placebo at baseline and mesenchymal stem cells at 6 months

Outcomes

Primary Outcome Measures

Neurophysiological parameters - Combined evoked potentials
Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV)

Secondary Outcome Measures

Neurophysiological parameters - Somatosensoric evoked potantials
SEP, latency (ms) and amplitude (mV)
Neurophysiological parameters - Motor evoked potentials
MEP, latency (ms) and amplitude (mV)
Neurophysiological parameters - Visual evoked potentials
VEP, latency (ms) and amplitude (mV)
MRI-Lesion volumes
T1- and T2-weighted hyperintense lesion volume
MR- Brain volumes
Brain volumes
Expanded disability status scale
EDSS
Patient reported outcomes (PROs)
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS)
Nine-Hole-Peg Test (9-HPT)
Nine-Hole-Peg Test (9-HPT)
Timed 25 Foot Walk (T25FW)
Timed 25 Foot Walk (T25FW)
Visual function
Visual acuity, visual field, color vision and contrast sensitivity
Optical coherence tomography (OCT)
Retinal thickness
Rate and nature of adverse- and serious adverse events
Adverse events

Full Information

First Posted
January 20, 2021
Last Updated
September 8, 2023
Sponsor
Haukeland University Hospital
Collaborators
University of Bergen, University Hospital Ulm, University Hospital, Akershus, St. Olavs Hospital, University Hospital of North Norway
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1. Study Identification

Unique Protocol Identification Number
NCT04749667
Brief Title
Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Acronym
SMART-MS
Official Title
Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 9, 2021 (Actual)
Primary Completion Date
October 4, 2024 (Anticipated)
Study Completion Date
January 4, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haukeland University Hospital
Collaborators
University of Bergen, University Hospital Ulm, University Hospital, Akershus, St. Olavs Hospital, University Hospital of North Norway

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective of the study is to investigate neuroregenerative efficacy (proof of concept) of intrathecal treatment with autologous MSCs as measured by neurophysiological parameters in patients with progressive MS. Secondary objectives are to assess neuroregenerative efficacy as measured by other neurophysiological parameters as well as clinical, opthalmological and MRI modalities, and to assess safety of the treatment procedure.
Detailed Description
Prospective, interventional, randomized, placebo-controlled, cross-over study. Patients are randomized to either treatment arm A or B. Patients in both treatment arms receive intrathecal autologous MSCs, arm A at baseline and arm B at six months. All patients undergo bone marrow (BM) aspiration prior to baseline. Patients in treatment arm A receive intrathecal autologous MSCs whereas patients in treatment arm B receive placebo. The treatment is blinded for the patients. The BM aspirate from patients in treatment arm B is processed, cryopreserved and stored in a biobank. At six months, all patients undergo a second BM aspiration. Patients in treatment arm A now receive placebo. The BM aspirate from patients in treatment arm A is processed, cryopreserved and stored in a biobank. Patients in treatment arm B receive intrathecal autologous MSCs. The treatment is blinded for the patients. Primary outcome is assessed at six months and secondary outcomes are assessed at six, twelve and eighteen months post baseline. Investigator assessing outcomes are blinded to patient treatment allocation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Progressive Multiple Sclerosis
Keywords
Mesenchymal stem cells, Multiple sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Model Description
Prospective, randomized, placebo-controlled, cross-over study
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A - Crossover with MSCs at baseline and placebo at 6 months
Arm Type
Experimental
Arm Description
Receives mesenchymal stem cells at baseline and placebo at 6 months
Arm Title
Arm B - Crossover with placebo at baseline and MSCs at 6 months
Arm Type
Experimental
Arm Description
Receives placebo at baseline and mesenchymal stem cells at 6 months
Intervention Type
Other
Intervention Name(s)
MSCs
Other Intervention Name(s)
Mesenchymal stem cells
Intervention Description
Autologous bone-marrow derived mesenchymal stem cells
Intervention Type
Drug
Intervention Name(s)
Saline
Intervention Description
Isotonic saline
Primary Outcome Measure Information:
Title
Neurophysiological parameters - Combined evoked potentials
Description
Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Neurophysiological parameters - Somatosensoric evoked potantials
Description
SEP, latency (ms) and amplitude (mV)
Time Frame
6 and 12 months
Title
Neurophysiological parameters - Motor evoked potentials
Description
MEP, latency (ms) and amplitude (mV)
Time Frame
6 and 12 months
Title
Neurophysiological parameters - Visual evoked potentials
Description
VEP, latency (ms) and amplitude (mV)
Time Frame
6 and 12 months
Title
MRI-Lesion volumes
Description
T1- and T2-weighted hyperintense lesion volume
Time Frame
6 and 12 months
Title
MR- Brain volumes
Description
Brain volumes
Time Frame
6 and 12 months
Title
Expanded disability status scale
Description
EDSS
Time Frame
6, 12 and 18 months
Title
Patient reported outcomes (PROs)
Description
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS)
Time Frame
6, 12 and 18 months
Title
Nine-Hole-Peg Test (9-HPT)
Description
Nine-Hole-Peg Test (9-HPT)
Time Frame
6, 12 and 18 months
Title
Timed 25 Foot Walk (T25FW)
Description
Timed 25 Foot Walk (T25FW)
Time Frame
6, 12 and 18 months
Title
Visual function
Description
Visual acuity, visual field, color vision and contrast sensitivity
Time Frame
6, 12 and 18 months
Title
Optical coherence tomography (OCT)
Description
Retinal thickness
Time Frame
6, 12 and 18 months
Title
Rate and nature of adverse- and serious adverse events
Description
Adverse events
Time Frame
6, 12 and 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥18 to ≤55, both genders Diagnosis of secondary progressive or primary progressive MS using revised McDonald criteria of clinically definite MS An EDSS score of 4 to 7 Disease duration 2 - 15 years Signed, written informed consent Exclusion Criteria: Any illness or prior/ongoing treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate autologous stem cell treatment Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity Current immunomodulatory/immunosuppressive treatment Immunomodulatory/immunosuppressive treatment within 6 months prior to inclusion. This includes, but is not restricted to treatment with natalizumab, fingolimod, dimetylfumurat, glatiramer acetate, interferon beta medications, teriflunomide, and siponimod. Treatment with kladribin, ocrelizumab, rituximab, and alemtuzumab within 12 months prior to inclusion Treatment with hematopoietic stem cell therapy within 12 months prior to inclusion Treatment with glucocorticoids or ACTH within three months prior to start of inclusion Having experienced an MS relapse within 2 years prior to study inclusion Current treatment with fampridin History of malignancy other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year Severely limited life expectancy by another co-morbid illness History of previous diagnosis of myelodysplasia or previous hematologic disease (including lymphoproliferative disease, bone marrow insufficiency or previous lymphoid irradiation) or current clinically relevant abnormalities of white blood cell counts Immunocompromised patients Estimated glomerular filtration rate <60 ml/min/1.73 m2 or known renal failure Bleeding or clotting diathesis or the use of antithrombotic or anticoagulative treatment Platelet (thrombocyte) count <100 x 10*9/L Participation in another experimental clinical study within the preceding 12 months Contraindications to MRI Prior or current major depression Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol. Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study), breastfeeding or lactation History of autologous/allogenic bone marrow transplantation or peripheral blood cell transplant Known hypersensitivity against paracetamol, codein or xylocain Diagnosis or strong suspicion of polyneuropathy Prior or current alcohol or drug dependencies Inability to give informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher Elnan Kvistad, PhD
Organizational Affiliation
Haukeland University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lars Bø, Prof
Organizational Affiliation
Haukeland University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
University hospital of North Norway
City
Tromsø
State/Province
Troms Og Finnmark
Country
Norway
Facility Name
St.Olav university hospital
City
Trondheim
State/Province
Trøndelag
Country
Norway
Facility Name
Haukeland University Hospital
City
Bergen
State/Province
Vestland
Country
Norway
Facility Name
Akershus university hospital
City
Lørenskog
State/Province
Viken
Country
Norway

12. IPD Sharing Statement

Learn more about this trial

Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis

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