Clinical trial NCT04749667: Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Official title: Study of Mesenchymal Autologous Stem Cells as Regenerative Treatment for Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Progressive Multiple Sclerosis
Keywords: Mesenchymal stem cells
Multiple sclerosis
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: University of Bergen
name: University Hospital Ulm
name: University Hospital, Akershus
name: St. Olavs Hospital
name: University Hospital of North Norway
First posted: 2021-02-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Prospective, randomized, placebo-controlled, cross-over study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Neurophysiological parameters - Combined evoked potentials
timeFrame: 6 months
Secondary outcomes:
measure: Neurophysiological parameters - Somatosensoric evoked potantials
timeFrame: 6 and 12 months
measure: Neurophysiological parameters - Motor evoked potentials
timeFrame: 6 and 12 months
measure: Neurophysiological parameters - Visual evoked potentials
timeFrame: 6 and 12 months
measure: MRI-Lesion volumes
timeFrame: 6 and 12 months
measure: MR- Brain volumes
timeFrame: 6 and 12 months
measure: Expanded disability status scale
timeFrame: 6, 12 and 18 months
measure: Patient reported outcomes (PROs)
timeFrame: 6, 12 and 18 months
measure: Nine-Hole-Peg Test (9-HPT)
timeFrame: 6, 12 and 18 months
measure: Timed 25 Foot Walk (T25FW)
timeFrame: 6, 12 and 18 months
measure: Visual function
timeFrame: 6, 12 and 18 months
measure: Optical coherence tomography (OCT)
timeFrame: 6, 12 and 18 months
measure: Rate and nature of adverse- and serious adverse events
timeFrame: 6, 12 and 18 months
Other outcomes:
Locations:
city: Tromsø
country: Norway
facility: University hospital of North Norway
state: Troms Og Finnmark
city: Trondheim
country: Norway
facility: St.Olav university hospital
state: Trøndelag
city: Bergen
country: Norway
facility: Haukeland University Hospital
state: Vestland
city: Lørenskog
country: Norway
facility: Akershus university hospital
state: Viken
Study officials:
affiliation: Haukeland University Hospital
name: Christopher Elnan Kvistad, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Lars Bø, Prof
role: STUDY_CHAIR
References: