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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Progressive Multiple Sclerosis; Multiple Sclerosis
• Intervention / Treatment: Other: MSCs; Drug: Saline

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Christopher Elnan Kvistad, PhD; Phone Number: 0047 559750000; Email: echr@helse-bergen.no
• Study Contact Backup: Name: Lars Bø, Prof; Phone Number: 0047 559750000; Email: lars.bo@helse-bergen.no

Study Locations

• Norway
  • Troms Og Finnmark
    • Tromsø, Troms Og Finnmark, Norway
      • University Hospital of North Norway
  • Trøndelag
    • Trondheim, Trøndelag, Norway
      • St.Olav university hospital
  • Vestland
    • Bergen, Vestland, Norway
      • Haukeland University Hospital
  • Viken
    • Lørenskog, Viken, Norway
      • Akershus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Crossover with MSCs at baseline and placebo at 6 months; Receives mesenchymal stem cells at baseline and placebo at 6 months	Other: MSCs; Autologous bone-marrow derived mesenchymal stem cells; Other Names: Mesenchymal stem cells; Drug: Saline; Isotonic saline
Experimental: Arm B - Crossover with placebo at baseline and MSCs at 6 months; Receives placebo at baseline and mesenchymal stem cells at 6 months	Other: MSCs; Autologous bone-marrow derived mesenchymal stem cells; Other Names: Mesenchymal stem cells; Drug: Saline; Isotonic saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurophysiological parameters - Combined evoked potentials	Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurophysiological parameters - Somatosensoric evoked potantials	SEP, latency (ms) and amplitude (mV)	6 and 12 months
Neurophysiological parameters - Motor evoked potentials	MEP, latency (ms) and amplitude (mV)	6 and 12 months
Neurophysiological parameters - Visual evoked potentials	VEP, latency (ms) and amplitude (mV)	6 and 12 months
MRI-Lesion volumes	T1- and T2-weighted hyperintense lesion volume	6 and 12 months
MR- Brain volumes	Brain volumes	6 and 12 months
Expanded disability status scale	EDSS	6, 12 and 18 months
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)	6, 12 and 18 months
Nine-Hole-Peg Test (9-HPT)	Nine-Hole-Peg Test (9-HPT)	6, 12 and 18 months
Timed 25 Foot Walk (T25FW)	Timed 25 Foot Walk (T25FW)	6, 12 and 18 months
Visual function	Visual acuity, visual field, color vision and contrast sensitivity	6, 12 and 18 months
Optical coherence tomography (OCT)	Retinal thickness	6, 12 and 18 months
Rate and nature of adverse- and serious adverse events	Adverse events	6, 12 and 18 months

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: University Hospital of North Norway; University of Bergen; St. Olavs Hospital; University Hospital, Akershus; University Hospital Ulm
• Investigators: Principal Investigator: Christopher Elnan Kvistad, PhD, Haukeland University Hospital; Study Chair: Lars Bø, Prof, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Estimated): October 4, 2024
• Study Completion (Estimated): January 4, 2025

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Mesenchymal stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis
• Other Study ID Numbers: 159326

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No