Multiple Sclerosis, Progressive Multiple Sclerosis
Conditions
Keywords
Mesenchymal stem cells, Multiple sclerosis
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.
Interventions
OTHERMSCs
Autologous bone-marrow derived mesenchymal stem cells
DRUGSaline
Isotonic saline
Sponsors
Haukeland University Hospital
University of Bergen
University Hospital Ulm
University Hospital, Akershus
University Hospital of North Norway
St. Olavs Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
Prospective, randomized, placebo-controlled, cross-over study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurophysiological parameters - Combined evoked potentials | 6 months | Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurophysiological parameters - Somatosensoric evoked potantials | 6 and 12 months | SEP, latency (ms) and amplitude (mV) |
| Neurophysiological parameters - Motor evoked potentials | 6 and 12 months | MEP, latency (ms) and amplitude (mV) |
| Neurophysiological parameters - Visual evoked potentials | 6 and 12 months | VEP, latency (ms) and amplitude (mV) |
| MRI-Lesion volumes | 6 and 12 months | T1- and T2-weighted hyperintense lesion volume |
| MR- Brain volumes | 6 and 12 months | Brain volumes |
| Expanded disability status scale | 6, 12 and 18 months | EDSS |
| Patient reported outcomes (PROs) | 6, 12 and 18 months | 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) | 6, 12 and 18 months | Nine-Hole-Peg Test (9-HPT) |
| Timed 25 Foot Walk (T25FW) | 6, 12 and 18 months | Timed 25 Foot Walk (T25FW) |
| Visual function | 6, 12 and 18 months | Visual acuity, visual field, color vision and contrast sensitivity |
| Optical coherence tomography (OCT) | 6, 12 and 18 months | Retinal thickness |
| Rate and nature of adverse- and serious adverse events | 6, 12 and 18 months | Adverse events |
Countries
Norway
Contacts
PRINCIPAL_INVESTIGATORChristopher Elnan Kvistad, PhD
Haukeland University Hospital
STUDY_CHAIRLars Bø, Prof
Haukeland University Hospital
Outcome results
None listed