Intrathecal Administration of Autologous Mesenchymal Stem Cell-derived Neural Progenitors (MSC-NP) in Progressive Multiple Sclerosis

NCT ID: NCT03355365

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-21
• Study Completion Date: 2023-04-17

Brief Summary

This is a phase II, double-blinded, placebo-controlled, randomized, cross-over Study designed to determine the efficacy of multiple intrathecal administrations of autologous mesenchymal stem cell-derived neural progenitor cells (MSC-NP) compared to placebo in patients with progressive multiple sclerosis. Efficacy will be measured through assessment of disability outcomes. Study participants will receive six intrathecal injections of culture-expanded autologous MSC-NPs at two month intervals in one year and six lumbar punctures as placebo treatments in a second year.

Detailed Description

The IT-MSC-NP treatments and all clinical assessments will take place at a single center (Tisch MSRCNY). Study subjects will be assigned to blocks stratified by baseline EDSS score (3.0-4.0, 4.5-5.5, 6.0, and 6.5) and disease subtype (SPMS or PPMS). Study subjects are randomized in an equal fashion (1:1) to study treatment and placebo at initial randomization. Subjects in each block will be randomized into placebo or treatment group. In the second year, treated subjects will cross over to the placebo group and placebo subjects will cross over to the treated group.

The total study duration will be 3 years upon enrollment. Each study subject will be required to attend up to 18 study visits, to include 1 screening visit, 1 bone marrow visit, 1 baseline visit, followed by study visits every 2 months during the treatment period of two years (12 treatment/LP procedure visits and 2 outcome visits), and an additional follow-up visit at the end of year 3.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intrathecal MSC-NP injection

Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.

Group Type: EXPERIMENTAL

Intrathecal MSC-NP injection

Intervention Type: BIOLOGICAL

MSC-NPs represent a neural subpopulation of MSCs from bone marrow with reduced pluripotency and minimized risk of ectopic differentiation, thus are likely to be more suitable for CNS delivery. Importantly, characterization of MSC-NPs demonstrated their immunoregulatory and trophic properties, and MSC-NPs derived from MS and non-MS patients alike were therapeutically viable.

Intrathecal saline injection

Patients will receive six placebo injections through spinal taps every 2 months over a year.

Group Type: PLACEBO_COMPARATOR

Intrathecal saline injection

Intervention Type: OTHER

Placebo

Interventions

Intrathecal MSC-NP injection

MSC-NPs represent a neural subpopulation of MSCs from bone marrow with reduced pluripotency and minimized risk of ectopic differentiation, thus are likely to be more suitable for CNS delivery. Importantly, characterization of MSC-NPs demonstrated their immunoregulatory and trophic properties, and MSC-NPs derived from MS and non-MS patients alike were therapeutically viable.

Intervention Type: BIOLOGICAL

Intrathecal saline injection

Placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of MS as defined by the McDonald criteria
• Diagnosis of primary progressive or secondary progressive MS
• Between the ages of 18-65 years
• Significant disability shown by an Expanded Disability Status Score (EDSS) of greater than or equal to 3.0, and less than or equal to 6.5, that was not acquired within the last 12 months.
• Stable disease state as evidenced by a lack of gadolinium-enhancing lesions on an MRI and by a stable MRI disease burden (number of T2 lesions and size of lesions) in the last six months and no significant change in EDSS (1 point or more) in the last 12 months
• Must agree to undergo four MRIs: at the time of enrollment, after year 1, after year 2, and after year 3
• Patients either within the geographical area or who are able to arrange reliable travel during the study period

Exclusion Criteria

• EDSS greater than 6.5
• Duration of Disease >20 years at time of screening
• Change of disease modifying agent < 12 months prior to beginning treatment. Additionally, no changes in disease modifying agent will be made during the course of the study.
• Change in MS symptom management treatment < 6 months prior to beginning treatment. Additionally, no changes in MS symptom management treatments will be made during the course of the study, unless there has been clinical improvement, in which case, a patient may discontinue a medication.
• Start of any new orthotic device or durable medical equipment < 6 months prior to beginning treatment or during the course of the study (patients may discontinue use of these devices during the course of the study if they show clinical improvement).
• All patients who have ever been on Lemtrada (alemtuzumab)
• All patients who have had any prior stem cell treatments, including HSCT
• Pregnant or nursing mothers, or any woman intending to become pregnant in the next three years
• All patients will have screening blood tests done. Only patients whose values are in the normal range as determined by the laboratory norms based on age and sex will be allowed to participate. Exceptions may be made for borderline normal laboratory values manifesting no clinical symptoms at the discretion of the Principal Investigator.
• Use of systemic chemotherapeutic or anti-mitotic medications within three months of study start date due to the possibility of interference with bone marrow procedure
• Any patients with a history of or with active malignancy
• Use of steroids within three months of the study start date, as this would suggest an active disease state
• History of cirrhosis due to increased risk of central nervous system (CNS) infection
• Significantly uncontrolled hypertension because of increased risk for stroke or CNS hemorrhage.
• Patients with active thyroid disease resulting in hyperthyroidism or hypothyroidism (Only well controlled patients with labs in the normal range will be included) because of hormone influence on cell growth
• History of central nervous system infection or immunodeficiency syndromes due to increased risk of CNS infection
• Preexisting blood disease (such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia) due to invasive nature of bone-marrow aspiration
• Previous or current history of a coagulation disorder
• Any metal implant in the body, which is contraindicated for MRI studies
• Patients with alcohol or other substance abuse problems that may affect stem cell growth; habitual drug (including marijuana and nicotine) abusers, will be excluded from the study
• Other major disease that, in the opinion of the Principal Investigator, would preclude participation in the study
• Patients with Hepatitis B (HBV), Hepatitis C (HCV), syphilis, HIV-1, or HIV-2.
• Any evidence of significant cognitive dysfunction based on a screening history and physical examination because it would preclude giving a truly informed consent
• Patients who are enrolled in another clinical trial for MS treatment or who have received any study drug/biologics within the last 6 months. Additionally, while in the trial, patients may not enroll in any other clinical trial for MS or any other condition.
• Patients who are anticipated to have difficultly accessing the intrathecal space related to scoliosis, obesity, or any other relevant factors determined by the PI.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tisch Multiple Sclerosis Research Center of New York

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saud A Sadiq, MD, FAAN

Role: PRINCIPAL_INVESTIGATOR

Tisch MS Research Center of New York

Locations

Tisch MS Research Center of New York

New York, New York, United States

Countries

United States

References

Harris VK, Stark J, Vyshkina T, Blackshear L, Joo G, Stefanova V, Sara G, Sadiq SA. Phase I Trial of Intrathecal Mesenchymal Stem Cell-derived Neural Progenitors in Progressive Multiple Sclerosis. EBioMedicine. 2018 Mar;29:23-30. doi: 10.1016/j.ebiom.2018.02.002. Epub 2018 Feb 3.

Reference Type: BACKGROUND

PMID: 29449193 (View on PubMed)

Harris VK, Stark J, Williams A, Roche M, Malin M, Kumar A, Carlson AL, Kizilbash C, Wollowitz J, Andy C, Gerber LM, Sadiq SA. Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial. Stem Cell Res Ther. 2024 May 23;15(1):151. doi: 10.1186/s13287-024-03765-6.

Reference Type: RESULT

PMID: 38783390 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

TISCHMS-MSCNP-002

Identifier Type: -

Identifier Source: org_study_id