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

Phase 2

Completed

Conditions: Multiple Sclerosis

Interventions: Biological: Intrathecal MSC-NP injection
Other: Intrathecal saline injection

Registration Number: NCT03355365

Lead Sponsor: Tisch Multiple Sclerosis Research Center of New York

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Intrathecal MSC-NP injection	Intrathecal MSC-NP injection	Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.
Intrathecal saline injection	Intrathecal saline injection	Patients will receive six placebo injections through spinal taps every 2 months over a year.

Primary Outcome Measures

Name	Time	Method
Expanded Disability Status Scale (EDSS) Plus	Baseline and 13 months	Changes in disability assessed based on composite score of EDSS, timed 25-foot walk (T25FW), and nine hole peg test (9HPT) (EDSS-Plus). Improvement is defined by at least one of the following three measures: ≥0.5 decrease in EDSS (if EDSS at entry is ≥ 6.0) or ≥ 1.0 decrease in EDSS (if EDSS at entry is ≤5.5), ≥20% increase in T25FW, or ≥20% increase in 9HPT in either dominant or non-dominant hand. Assessments were made at baseline and month 13. The number of patients who improved in any of the 3 composite measures in month 13 compared to baseline is reported.

Secondary Outcome Measures

Name	Time	Method
Percent Change in T25FW (Timed 25 Foot Walk) From Baseline	Baseline and 13 months	The timed 25-foot walk (T25FW) is a test used in multiple sclerosis (MS) to assess a person's mobility and leg function, where individuals walk 25 feet as quickly and safely as possible, and the time taken is recorded. A positive percentage change indicates improved walking in month 13 compared to baseline, whereas a negative percentage change indicates worsening.
Percent Change in 6MWT (6 Minute Walk Test) From Baseline	Baseline and 13 months	The 6-minute walk test (6MWT) in multiple sclerosis (MS) measures functional walking capacity by assessing the distance a person can walk in 6 minutes. A positive percentage change indicates improved walking capacity at month 13 compared to baseline, whereas a negative percentage change indicates worsening.
Change in MSWS-12 (12 Item MS Walking Scale) Score From Baseline	Baseline and 13 months	The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome measure that assesses the impact of multiple sclerosis (MS) on walking ability. The self-administered questionnaire consists of 12 items addressing how MS has affected various aspects of walking over the past two weeks. Each of the 12 items is scored from 1 to 5 from: 1 = Not at all to 5 = Extremely. Raw total score ranges from 12 (no impairment) to 60 (maximum impairment). Raw score is converted to a standardized score (0-100 scale) producing a final score from 0 = No impact of MS on walking to 100 = Maximum impact. The change in score from baseline to post-intervention was calculated. A decrease in score at month 13 compared to baseline was considered improvement.
Change in PASAT (Paced Auditory Serial Addition Test) Score From Baseline	Baseline and 13 months	The Paced Auditory Serial Addition Test (PASAT) is a neuropsychological test used to assess cognitive impairments, attention, information processing speed, and working memory. The test involves listening to a series of single-digit numbers and the individual must add each new number to the one immediately before it. The score is the number of correct responses out of 60 items. The change in score from baseline to post-intervention is calculated. A positive change in score means an increase in the number of correct answers at month 13 compared to baseline, generally indicating improvement in information processing speed and sustained attention.
Change in Multiple Sclerosis Functional Composite (MSFC) Z-Score From Baseline	Baseline and 13 months	The Multiple Sclerosis Functional Composite (MSFC) is a standardized tool used to quantify disability in people with multiple sclerosis (MS) by measuring leg function/ambulation (timed 25 foot walk), arm/hand function (9-hole peg test), and cognitive function (Paced Auditory Serial Addition Test). Each assessment is converted into a Z score. A Z-score of 0 represents the population mean. The composite MSFC Z-score represents an average of the 3 Z-scores. A positive change in composite Z-score in month 13 compared to baseline represents better performance and a negative change in composite Z score indicates worse performance.
Change in EDSS From Baseline	Baseline and 13 months	The Expanded Disability Status Scale (EDSS) is a standardized measure used to assess and track the level of disability in people with multiple sclerosis (MS), ranging from 0 (normal neurological status) to 10 (death due to MS) in 0.5 increments. Only ambulatory subjects were enrolled in this study with an EDSS between 3.0 and 6.5. Subgroups of participants were analyzed based on the degree of walking disability. EDSS 3.0-5.5 represents moderate to severe disability but able to walk without assistance, and EDSS 6.0-6.5 represents a need for unilateral or bilateral assistance to ambulate. A decrease in EDSS at month 13 compared to baseline is considered improvement.
Percent Change in 9HPT-D (9 Hole Peg Test in Dominant Hand) From Baseline	Baseline and 13 months	The Nine-Hole Peg Test (9HPT) is a standardized, quantitative assessment used to measure manual dexterity and upper extremity function in individuals with multiple sclerosis (MS). Each hand, dominant (D) and non-dominant (ND) is assessed seperately. A positive percentage change indicates improved function at month 13 compared to baseline, whereas a negative percentage change indicates worsening.
Percent Change in 9HPT-ND (9 Hole Peg Test in Non-Dominant Hand) From Baseline	Baseline and 13 months	The Nine-Hole Peg Test (9HPT) is a standardized, quantitative assessment used to measure manual dexterity and upper extremity function in individuals with multiple sclerosis (MS). Each hand, dominant (D) and non-dominant (ND) is assessed seperately. A positive percentage change indicates improved function at month 13 compared to baseline, whereas a negative percentage change indicates worsening.

Trial Locations

Locations (1): Tisch MS Research Center of New York
🇺🇸
New York, New York, United States
Tisch MS Research Center of New York
🇺🇸New York, New York, United States