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

NCT01933802 | Completed Phase 1 DMC

• 2 other identifiers: TISCHMS-MSCNP-001IND 13889
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The study is an open-label, phase I clinical trial designed to evaluate the safety and tolerability of intrathecal administration of autologous mesenchymal stem cell-derived neural progenitor cells (MSC-NP) in patients with progressive multiple sclerosis. Study participants will receive three intrathecal injections of culture-expanded autologous MSC-NPs at three month intervals.

Conditions

Multiple Sclerosis

Keywords

mesenchymal stem cells; neural progenitors; autologous; bone marrow; multiple sclerosis

Outcome Measures

Primary Outcomes (2)

• Number of participants with adverse events

  The primary objective of the study is to assess the safety and tolerability of intrathecal therapy with autologous MSCNPs in MS. Number of participants with adverse events will be documented 1 day, 1 week, 1 month and 2 months post treatment for three treatments (followup for third treatment is 3 months instead of 2 months).

  9 months

• Number of participants with adverse events .

  The co-primary objective will be to observe long term safety of the treatment 6 months and 30 months following the last treatment.

  30 months

Secondary Outcomes (1)

• Preliminary evaluation of efficacy

  9 months

Study Arms (1)

autologous MSC-NP

EXPERIMENTAL

intrathecal administration of autologous MSC-NP in three doses at three month intervals

Biological: intrathecal administration of autologous MSC-NP

Interventions

intrathecal administration of autologous MSC-NP BIOLOGICAL

Autologous MSC-NPs administered intrathecally at a dose between 2 and 10 million cells, depending on ex vivo expansion characteristics. Three doses will be administered at 3 month intervals.

autologous MSC-NP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MS as defined by the McDonald criteria
• Diagnosis of primary progressive or secondary progressive MS
• Between the ages of 18-70 years
• Significant disability shown by an Expanded Disability Status Score (EDSS) of 3.0 or greater 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 MRIs at the time of enrollment, 2 months after the first treatment, and 27 months after the last treatment
• Live in northern New Jersey, southern New York, or southwestern Connecticut during the study period, or patients must be able to arrange reliable travel accommodations to be present for every study visit if they live farther away.

You may not qualify if:

• Pregnant or nursing mothers or any woman intending to become pregnant in the next three years
• All patients will have pre-study liver function tests, PT/PPT, platelets, hematocrit, and renal function laboratory 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.
• 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 a highly active disease state
• History of cirrhosis due to increased risk of central nervous system (CNS) infection
• Poorly controlled hypertension because of increased risk for stroke or CNS hemorrhage. Specifically, any patient with a systolic blood pressure value of ≥ 145 mm/Hg or a diastolic blood pressure value of ≥ 95 mm/Hg will be excluded from study participation.
• History of thyroid disorders or other endocrine disorders 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 in the body, which is contraindicated for MRI studies
• Allergy to any of the antibiotics used in this study, e.g. tobramycin, vancomycin, or gentamicin
• Patients with alcohol or other substance abuse problems
• Other major disease that, in the opinion of the Principal Investigator, would preclude participation in the study

Sponsors & Collaborators

• Tisch Multiple Sclerosis Research Center of New York: lead

Study Sites (1)

Tisch MS Research Center of New York

New York, New York, 10019, United States

Location

Related Publications (4)

• Harris VK, Faroqui R, Vyshkina T, Sadiq SA. Characterization of autologous mesenchymal stem cell-derived neural progenitors as a feasible source of stem cells for central nervous system applications in multiple sclerosis. Stem Cells Transl Med. 2012 Jul;1(7):536-47. doi: 10.5966/sctm.2012-0015. Epub 2012 Jun 28.

  PMID: 23197858 BACKGROUND

• Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci. 2012 Feb 15;313(1-2):167-77. doi: 10.1016/j.jns.2011.08.036. Epub 2011 Oct 1.

  PMID: 21962795 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.

  PMID: 29449193 RESULT

• Harris VK, Stark JW, Yang S, Zanker S, Tuddenham J, Sadiq SA. Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 4;8(1):e928. doi: 10.1212/NXI.0000000000000928. Print 2021 Jan.

  PMID: 33277427 DERIVED

Related Links

• Tisch MS Research Center of New York

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Saud A Sadiq, MD

  Tisch MS Research Center of New York

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2013
• First Posted: September 2, 2013
• Study Start: April 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: March 1, 2017
• Last Updated: March 19, 2018

Record last verified: 2018-03

Locations

US (1)