Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- MSCs
- Conditions
- Multiple Sclerosis
- Sponsor
- Haukeland University Hospital
- Enrollment
- 18
- Locations
- 4
- Primary Endpoint
- Neurophysiological parameters - Combined evoked potentials
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
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.
Investigators
Eligibility 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
Arms & Interventions
Arm A - Crossover with MSCs at baseline and placebo at 6 months
Receives mesenchymal stem cells at baseline and placebo at 6 months
Intervention: MSCs
Arm A - Crossover with MSCs at baseline and placebo at 6 months
Receives mesenchymal stem cells at baseline and placebo at 6 months
Intervention: Saline
Arm B - Crossover with placebo at baseline and MSCs at 6 months
Receives placebo at baseline and mesenchymal stem cells at 6 months
Intervention: MSCs
Arm B - Crossover with placebo at baseline and MSCs at 6 months
Receives placebo at baseline and mesenchymal stem cells at 6 months
Intervention: Saline
Outcomes
Primary Outcomes
Neurophysiological parameters - Combined evoked potentials
Time Frame: 6 months
Somatosensoric evoked potentials (SEP) + visual evoked potentials (VEP) + motor evoked potentials (MEP), latency (ms) and amplitude (mV)
Secondary Outcomes
- MR- Brain volumes(6 and 12 months)
- Expanded disability status scale(6, 12 and 18 months)
- Neurophysiological parameters - Somatosensoric evoked potantials(6 and 12 months)
- Neurophysiological parameters - Motor evoked potentials(6 and 12 months)
- Visual function(6, 12 and 18 months)
- Rate and nature of adverse- and serious adverse events(6, 12 and 18 months)
- Neurophysiological parameters - Visual evoked potentials(6 and 12 months)
- MRI-Lesion volumes(6 and 12 months)
- Patient reported outcomes (PROs)(6, 12 and 18 months)
- Nine-Hole-Peg Test (9-HPT)(6, 12 and 18 months)
- Timed 25 Foot Walk (T25FW)(6, 12 and 18 months)
- Optical coherence tomography (OCT)(6, 12 and 18 months)