Intrathecal Administration of Autologous Mesenchymal Stem... | NCT03355365

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Intrathecal MSC-NP injection	Experimental	Patients will receive six autologous stem cell injections through spinal taps every 2 months over a year.	Biological: Intrathecal MSC-NP injection
Intrathecal saline injection	Placebo Comparator	Patients will receive six placebo injections through spinal taps every 2 months over a year.	Other: Intrathecal saline injection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Intrathecal MSC-NP injection	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Expanded Disability Status Scale (EDSS) Plus	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.	Baseline and 13 months

Secondary Outcomes

Measure	Description	Time Frame
Change in Multiple Sclerosis Functional Composite (MSFC) Z-Score From Baseline	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.

Eligibility Module

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.

Name	Affiliation	Role
Saud A Sadiq, MD, FAAN	Tisch MS Research Center of New York	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Tisch MS Research Center of New York		New York	New York	10019	United States

PubMed Identifier	Type	Citation	Retractions
29449193	Background	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.
38783390	Result	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.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment First, Then Placebo	Participants will receive six autologous stem cell injections through spinal taps every 2 months over a year. After a period of 3 months, participants will crossover into the placebo group and receive six intrathecal injections of saline every 2 months over a year.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 26, 2021	Feb 18, 2025

ID	Title	Description
BG000	Treatment First, Then Placebo	Participants will receive six intrathecal injections of autologous stem cells every 2 months over a year. After a 3 month pause, participants will crossover into the placebo group and receive six intrathecal injections of saline every 2 months over a year.
BG001	Placebo First, Then Treatment	Participants will receive six intrathecal injections of saline every 2 months over a year. After a 3 month pause, participants will crossover into the treatment group and receive six intrathecal injections of autologous stem cells every 2 months over a year.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00027 BG00127 BG00254

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG00017 OG00117

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Fisher Exact		1.0														Superiority

Secondary

Change in Multiple Sclerosis Functional Composite (MSFC) Z-Score From Baseline

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.

Posted

Mean

Standard Deviation

change in composite z score

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)

Secondary

Change in EDSS From Baseline

Posted

Mean

Standard Deviation

change in score on a scale

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)	Participants received six intrathecal injections of saline every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants received placebo either first in the sequence (placebo first, then treatment) or second in the sequence (treatment first, then placebo).

Secondary

Percent Change in T25FW (Timed 25 Foot Walk) From Baseline

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.

Posted

Mean

Standard Deviation

% change

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)	Participants received six intrathecal injections of saline every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants received placebo either first in the sequence (placebo first, then treatment) or second in the sequence (treatment first, then placebo).

Secondary

Percent Change in 6MWT (6 Minute Walk Test) From Baseline

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.

Posted

Mean

Standard Deviation

% change

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)	Participants received six intrathecal injections of saline every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants received placebo either first in the sequence (placebo first, then treatment) or second in the sequence (treatment first, then placebo).

Secondary

Percent Change in 9HPT-D (9 Hole Peg Test in Dominant Hand) From Baseline

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.

Posted

Mean

Standard Deviation

% change

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)	Participants received six intrathecal injections of saline every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants received placebo either first in the sequence (placebo first, then treatment) or second in the sequence (treatment first, then placebo).

Secondary

Percent Change in 9HPT-ND (9 Hole Peg Test in Non-Dominant Hand) From Baseline

Posted

Mean

Standard Deviation

% change

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)	Participants received six intrathecal injections of saline every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants received placebo either first in the sequence (placebo first, then treatment) or second in the sequence (treatment first, then placebo).

Secondary

Change in MSWS-12 (12 Item MS Walking Scale) Score From Baseline

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.

Posted

Mean

Standard Deviation

change in score

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)

Secondary

Change in PASAT (Paced Auditory Serial Addition Test) Score From Baseline

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.

Posted

Mean

Standard Deviation

change in score

Baseline and 13 months

ID	Title	Description
OG000	Treatment (IT MSC-NP)	Participants received six intrathecal injections of autologous stem cells every 2 months over a year. Assessments were made 3 months after the last injection and compared to baseline. As part of the crossover study, participants were treated either first in the sequence (treatment first, then placebo) or second in the sequence (placebo first, then treatment).
OG001	Placebo (IT Saline)

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Intrathecal MSC-NP Injection (Year 1)	Patients will receive six autologous stem cell injections through spinal taps every 2 months in year 1.	27	2	27	24	27
EG001	Intrathecal Saline Injection (Year 1)	Patients will receive six placebo injections through spinal taps every 2 months in year 1. Intrathecal saline injection: Placebo	27	0	27	15	27
EG002	Intrathecal MSC-NP Injection (Year 2)	Compassionate crossover design with subjects who were treated with saline/placebo in year 1 received MSC-NP injections in year 2.	27	3	27	20	27
EG003	Intrathecal Saline Injection (Year 2)	Compassionate crossover design with subjects who were treated with MSC-NP in year 1 received saline injections in year 2.	24	3	24	13	24

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
infection	Infections and infestations	Non-systematic Assessment	Severe urinary tract infection and urosepsis requiring hospitalization.	EG0001 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG0030 affected24 at risk
hyperparathyroid	Endocrine disorders	Non-systematic Assessment	Previously undiagnosed hyperparathyroidism requiring parathyroidectomy. Chronic hypercalcemia contributed to urinary tract infection and sepsis.	EG0001 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
infection	Infections and infestations	Non-systematic Assessment	Lung infection associated with long COVID	EG0000 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
infection	Infections and infestations	Non-systematic Assessment	Acute appendicitis complicated by bowel perforation.	EG0000 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
Muscle weakness	Nervous system disorders	Non-systematic Assessment	Bilateral muscle weakness associated with MS progression	EG0000 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
pulmonary embolism	Blood and lymphatic system disorders	Non-systematic Assessment	Pulmonary embolism and deep vein thrombosis associated with long COVID	EG0000 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
COVID-19	Infections and infestations	Non-systematic Assessment	COVID-19 infection and severe urinary tract infection	EG0000 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
Cholecystitis	Infections and infestations	Non-systematic Assessment	Cholecystitis requiring cholecystectomy	EG0000 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Urinary tract infection	Infections and infestations	Non-systematic Assessment	EG0004 affected27 at risk EG0013 affected27 at risk EG0023 affected27 at risk EG0032 affected24 at risk
upper respiratory infection	Infections and infestations	Non-systematic Assessment	EG0001 affected27 at risk EG0012 affected27 at risk EG0026 affected27 at risk EG003
back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0011 affected27 at risk EG0021 affected27 at risk EG003
generalized muscle weakness	Nervous system disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0014 affected27 at risk EG0022 affected27 at risk EG003
Muscle weakness lower limb	Nervous system disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0011 affected27 at risk EG0020 affected27 at risk EG003
Cerebrospinal fluid leakage	Nervous system disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0011 affected27 at risk EG0021 affected27 at risk EG003
Graft vs host disease	Infections and infestations	Non-systematic Assessment	EG0000 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
rash	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0000 affected27 at risk EG0010 affected27 at risk EG0022 affected27 at risk EG003
allergic reaction	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0000 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
fever	General disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
diarrhea	Gastrointestinal disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0011 affected27 at risk EG0020 affected27 at risk EG003
neck. pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
neuralgia	Nervous system disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0011 affected27 at risk EG0020 affected27 at risk EG003
paresthesia	Nervous system disorders	Non-systematic Assessment	EG0002 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
skin infection	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0011 affected27 at risk EG0020 affected27 at risk EG003
spasticity	Nervous system disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
trigeminal nerve disorder	Nervous system disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk EG0021 affected27 at risk EG003
vertigo	General disorders	Non-systematic Assessment	EG0001 affected27 at risk EG0010 affected27 at risk EG0020 affected27 at risk EG003
Headache	General disorders	Systematic Assessment	EG00018 affected27 at risk EG00113 affected27 at risk EG00218 affected27 at risk EG003

ID	Term
D020278	Demyelinating Autoimmune Diseases, CNS
D020274	Autoimmune Diseases of the Nervous System
D009422	Nervous System Diseases
D003711	Demyelinating Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases