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

Multiple Sclerosis Clinical Trial

— SMART-MS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04749667
• Other study ID #: 159326
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 9, 2021
• Est. completion date: January 4, 2025

Study information

• Verified date: September 2023
• Source: Haukeland University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: January 4, 2025
• Est. primary completion date: October 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Progressive Multiple Sclerosis
• Sclerosis

Intervention

Other:
• MSCs
Autologous bone-marrow derived mesenchymal stem cells

Drug:
• Saline
Isotonic saline

Locations

Country	Name	City	State
Norway	Haukeland University Hospital	Bergen	Vestland
Norway	Akershus university hospital	Lørenskog	Viken
Norway	University hospital of North Norway	Tromsø	Troms Og Finnmark
Norway	St.Olav university hospital	Trondheim	Trøndelag

Sponsors (6)

Lead Sponsor	Collaborator
Haukeland University Hospital	St. Olavs Hospital, University Hospital of North Norway, University Hospital Ulm, University Hospital, Akershus, University of Bergen

Country where clinical trial is conducted

Norway, 

Outcome

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