SMART-MS: Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| 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:
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:
Drug: Saline
Isotonic saline
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
-
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
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University hospital of North Norway | Tromsø | Troms Og Finnmark | Norway | |
| 2 | St.Olav university hospital | Trondheim | Trøndelag | Norway | |
| 3 | Haukeland University Hospital | Bergen | Vestland | Norway | |
| 4 | Akershus university hospital | Lørenskog | Viken | Norway |
Sponsors and Collaborators
- Haukeland University Hospital
- University of Bergen
- University Hospital Ulm
- University Hospital, Akershus
- St. Olavs Hospital
- University Hospital of North Norway
Investigators
- Principal Investigator: Christopher Elnan Kvistad, PhD, Haukeland University Hospital
- Study Chair: Lars Bø, Prof, Haukeland University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 159326