Investigation of Intrathecal Autologous Mesenchymal Stromal Cells for Neuroregeneration in Progressive Multiple Sclerosis: A Controlled Clinical Trial
- Trial ID
- 2023-510228-63-00
- Sponsor
- Helse Bergen HF
Trial statistics
Diseases & Conditions
Objectives
The primary objective of the study is to investigate the **neuroregenerative** efficacy of intrathecal treatment with autologous mesenchymal stem cells (MSCs) in patients with progressive **multiple sclerosis**. This is measured by neurophysiological parameters, providing a proof of concept for the potential regenerative treatment. The clinical relevance of this objective lies in its potential to offer a novel therapeutic approach for progressive multiple sclerosis, a condition with limited treatment options.
Secondary objectives include assessing neuroregenerative efficacy through additional neurophysiological, ophthalmological, and MRI modalities, as well as evaluating the safety of the treatment. These objectives aim to provide a comprehensive understanding of the treatment's effects and ensure its safety profile.
Participants
The clinical trial involves participants diagnosed with **multiple sclerosis**, specifically those with secondary progressive or primary progressive forms of the disease, as defined by the revised McDonald criteria. The study population includes both male and female subjects, aged between 18 and 55 years, with an Expanded Disability Status Scale (EDSS) score ranging from 4 to 7. Participants have a disease duration of 2 to 18 years. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. All participants have provided signed, written informed consent. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the **neuroregenerative** efficacy and safety of intrathecal treatment with autologous **mesenchymal stem cells** (MSCs) in patients with progressive **multiple sclerosis** (MS). This study is a randomized, double-blind, controlled trial with a primary objective to assess the difference in combined evoked potentials (CEP) at six months compared to baseline between the MSC treatment group and the placebo group. The trial is expected to commence recruitment on January 1, 2025, and conclude by March 15, 2027, with an estimated duration of 18 months for each participant's involvement.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of secondary or primary progressive MS, and an Expanded Disability Status Scale (EDSS) score between 4 and 7. Following the screening, eligible participants will be randomized into two arms: one receiving the MSC treatment and the other receiving a placebo. The study will include follow-up visits at six and twelve months to evaluate primary and secondary endpoints, including differences in visual evoked potentials (VEP), somatosensory evoked potentials (SEP), and motor evoked potentials (MEP), as well as changes in MRI lesion volumes and clinical assessments such as the Nine-Hole Peg Test and Timed 25-Foot Walk.
The end-of-study visit will occur at the 18-month mark, where final assessments will be conducted to evaluate long-term safety and efficacy outcomes. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial will adhere to rigorous ethical standards, ensuring that all participants provide informed consent prior to enrollment. The study aims to provide valuable insights into the potential of MSCs as a regenerative treatment for progressive MS, contributing to the advancement of therapeutic options for this debilitating condition.
Treatment
The clinical trial involves the administration of two distinct treatments. The first treatment is **Sodium Chloride 0.9% w/v Intravenous Infusion BP**, which is a **solution for infusion**. This product is manufactured by B.BRAUN MELSUNGEN AG and is classified under the ATC code B05BB01, indicating its role as an electrolyte. The active substance, **sodium chloride**, is of chemical origin. The solution is administered via **intrathecal** route, with a maximum daily dose of 5 ml and a total dose not exceeding 5 ml over a treatment period of one day. This product serves as a comparator in the trial.
The second treatment involves the use of **Mesenchymal stem cells**, specifically **mesenchymal stromal cells, ex vivo cultured**. This product is provided by HELSE BERGEN and is administered as an **injection of intrathecal**. The active substance is a structurally diverse substance used in cell therapy, with synonyms including "ImmuStem" and "Ex vivo cultured human mesenchymal stromal cells." The administration follows the same dosing schedule as the sodium chloride solution, with a maximum daily and total dose of 5 ml over one day. This treatment is the test product in the trial, focusing on its neuroregenerative efficacy in patients with progressive multiple sclerosis.
Efficacy
The efficacy of the clinical trial titled "Study of Mesenchymal Autologous stem cells as Regenerative Treatment for Multiple Sclerosis (SMART-MS)" will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the difference in **Combined Evoked Potentials (CEP)**, which includes Visual Evoked Potentials (VEP), Somatosensory Evoked Potentials (SEP), and Motor Evoked Potentials (MEP), at 6 months compared to baseline between the treatment with mesenchymal stem cells (MSCs) and placebo.
Secondary endpoints will evaluate various parameters at 6 and 12 months, including differences in VEP, SEP, MEP, Expanded Disability Status Scale (EDSS), and MRI lesion volumes. Additional assessments will include brain volume, visual function, retinal thickness via Optical Coherence Tomography (OCT), and performance on the Nine-Hole-Peg Test (9-HPT) and Timed 25 Foot Walk (T25FW). Cognitive and quality of life measures will be assessed using the 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). Biomarker levels, such as serum neurofilament light chain and GFAP, will also be measured.
The trial will monitor intraindividual CEP changes longitudinally and document the rate and nature of adverse events over an 18-month follow-up period. Clinical relevance of changes in vital signs, physical examinations, and laboratory results will also be evaluated during this period. These assessments will provide comprehensive data on the neuroregenerative efficacy and safety of intrathecal treatment with autologous MSCs in patients with progressive Multiple Sclerosis.
Inclusion and Exclusion 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 - 18 years
- Signed, written informed consent
Exclusion Criteria
- Treatment with cytotoxic medications during the last 3 months prior to inclusion
- 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
- 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 within the last 10 years
- 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 with administration of another IMP within the preceding 12 months
- Contraindications to MRI
- Prior or current major depression
- 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
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Norway | Recruiting | 01 Jan 2025 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sodium Chloride 0.9 % w/v Intravenous Infusion BP | Comparator | INTRAVENOUS INFUSION | INTRATHECAL | 5 | 1 | PRD563980 |
Mesenchymal stem cells | Test | INJECTION OF INTRATHECAL | INTRATHECAL | 5 | 1 | PRD11083451 |