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

NCT ID: NCT04749667

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-09
• Study Completion Date: 2025-01-04

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.

Conditions

Multiple Sclerosis; Progressive Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Receives mesenchymal stem cells at baseline and placebo at 6 months

Group Type: EXPERIMENTAL

MSCs

Intervention Type: OTHER

Autologous bone-marrow derived mesenchymal stem cells

Saline

Intervention Type: DRUG

Isotonic saline

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

Receives placebo at baseline and mesenchymal stem cells at 6 months

Group Type: EXPERIMENTAL

MSCs

Intervention Type: OTHER

Autologous bone-marrow derived mesenchymal stem cells

Saline

Intervention Type: DRUG

Isotonic saline

Interventions

MSCs

Autologous bone-marrow derived mesenchymal stem cells

Intervention Type: OTHER

Saline

Isotonic saline

Intervention Type: DRUG

Other Intervention Names

Mesenchymal stem cells

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bergen

OTHER

Sponsor Role: collaborator

University Hospital Ulm

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: collaborator

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

Haukeland University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Elnan Kvistad, PhD

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Lars Bø, Prof

Role: STUDY_CHAIR

Haukeland University Hospital

Locations

Akershus university hospital

Lørenskog, Akershus, Norway

University hospital of North Norway

Tromsø, Troms Og Finnmark, Norway

St.Olav university hospital

Trondheim, Trøndelag, Norway

Haukeland University Hospital

Bergen, Vestland, Norway

Countries

Norway

Other Identifiers

159326

Identifier Type: -

Identifier Source: org_study_id