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Multiple SclerosisPhase 1/2SMART-MSNCT04749667

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

A Phase 1/2 study testing MSCs and Saline in people with Multiple Sclerosis and Progressive Multiple Sclerosis, run by Haukeland University Hospital at 4 sites in Norway.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years
What is being tested?
MSCs and Saline
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
4 sitesNorway
Study dates
9 Aug 2021to 15 Mar 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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

Trial locations and contacts

4 sites in 1 country.

Norway4 sites

  • Haukeland University Hospital

    Bergen, Vestland

  • Akershus university hospital

    Lørenskog, Akershus

  • University hospital of North Norway

    Tromsø, Troms Og Finnmark

  • St.Olav university hospital

    Trondheim, Trøndelag

Other trials in Norway

About this study

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.

Read the 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.

Being tested
MSCs, Saline
Keywords
Mesenchymal stem cells, Multiple sclerosis
Medical subject headings
Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive

What participants receive

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

  • MSCsOther

    Also called Mesenchymal stem cells

    Autologous bone-marrow derived mesenchymal stem cells

  • SalineDrug

    Isotonic saline

Study groups in NCT04749667
Study groupRoleWhat they receive
Arm A - Crossover with MSCs at baseline and placebo at 6 monthsExperimentalReceives mesenchymal stem cells at baseline and placebo at 6 months
Receives: Other: MSCs; Drug: Saline
Arm B - Crossover with placebo at baseline and MSCs at 6 monthsExperimentalReceives placebo at baseline and mesenchymal stem cells at 6 months
Receives: Other: MSCs; Drug: Saline

What is being measured

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

  1. Neurophysiological parameters - Combined evoked potentials

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

    Measured: 6 months

Secondary outcomes (12)

  1. Neurophysiological parameters - Somatosensoric evoked potantials

    SEP, latency (ms) and amplitude (mV)

    Measured: 6 and 12 months

  2. Neurophysiological parameters - Motor evoked potentials

    MEP, latency (ms) and amplitude (mV)

    Measured: 6 and 12 months

  3. Neurophysiological parameters - Visual evoked potentials

    VEP, latency (ms) and amplitude (mV)

    Measured: 6 and 12 months

  4. MRI-Lesion volumes

    T1- and T2-weighted hyperintense lesion volume

    Measured: 6 and 12 months

  5. MR- Brain volumes

    Brain volumes

    Measured: 6 and 12 months

  6. Expanded disability status scale

    EDSS

    Measured: 6, 12 and 18 months

  7. 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)

    Measured: 6, 12 and 18 months

  8. Nine-Hole-Peg Test (9-HPT)

    Nine-Hole-Peg Test (9-HPT)

    Measured: 6, 12 and 18 months

  9. Timed 25 Foot Walk (T25FW)

    Timed 25 Foot Walk (T25FW)

    Measured: 6, 12 and 18 months

  10. Visual function

    Visual acuity, visual field, color vision and contrast sensitivity

    Measured: 6, 12 and 18 months

  11. Optical coherence tomography (OCT)

    Retinal thickness

    Measured: 6, 12 and 18 months

  12. Rate and nature of adverse- and serious adverse events

    Adverse events

    Measured: 6, 12 and 18 months

Timeline

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

  1. First posted11 Feb 2021
  2. Study start9 Aug 2021
  3. Primary completion24 Mar 2025
  4. Study completion15 Mar 2027 (estimated)

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
Crossover
Model description
Prospective, randomized, placebo-controlled, cross-over study
Masking
Triple blind
Who is masked
Participant, Care provider, Outcomes assessor
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04749667
Sponsor's protocol ID
159326
Acronym
SMART-MS
Status last verified
Mar 2025
First submitted
20 Jan 2021
Last updated
12 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kvistad CE, Krakenes T, Holmoy T, Eidem LE, Steffensen L, Wesnes K, Rojewski M, Eichele T, Wergeland S, Gavasso S, Barsnes H, Assmus J, Al-Sharabi N, Mohamed-Ahmed S, Vrenken H, Brouwer I, Mutsaerts HM, Tranfa M, Gjerde C, Ytterdal M, Rodahl E, Berven FS, Schrezenmeier H, Mustafa K, Bo L. Intrathecal Mesenchymal Stem Cells in Progressive Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial (SMART-MS). Neurology. 2026 May 26;106(10):e214915. doi: 10.1212/WNL.0000000000214915. Epub 2026 May 4.

    PubMed 42081777

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MSCs and Saline in people with Multiple Sclerosis and Progressive Multiple Sclerosis, run by Haukeland University Hospital at 4 sites in Norway.

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 5 inclusion and 26 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: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Norway. 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?

This study is still under way. Results are not available in the source record yet.

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?

Neurophysiological parameters - Combined evoked potentials (time frame: 6 months). 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 NCT04749667, which also lists 1 linked publication.

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 12 Mar 2026.

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