A Study of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-M
An Open-label, Non-randomized, Phase I/II Study of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and Liberation Therapy (When Associated With CCSVI) in Patients With RRMS
What it found
A paper reports the results; we have not read it yet. See Papers below.
What was tested
Treatment tested
- Autologous Bone Marrow-Derived Mononuclear Stem Cells
- Liberation therapy
What it measured
Main measures
Proportion of patients with clinical improvement in EDSS score compared to baseline
Up to 12 months
Disability progressionProportion of patients with adverse events
up to 12 months
Safety
Other measures (9)
Proportion of patients with a change in either gadolinium enhancing or new T2-weighted lesions on brain MRI
12 months
MRI lesionsProportion of patients with reduction in T2 lesion volume on brain MRI
12 months
MRI lesionsProportion of patients with reduction in brain volume on MRI
12 months
MRI lesionsBrain volume lossProportion of patients with clinical improvement in EDSS score compared to baseline
3 months and 6 months
Disability progressionProportion of patients with clinical improvement in MSIS score compared to baseline
3 months, 6 months and 12 months
Quality of life (reported by participants)Proportion of patients with a change in mobility and leg function as measured by the 25 foot walking test
12 months
Walking and mobilityProportion of patients with a change in upper extremity function as measured by the Nine Hole Peg Test
12 months
Arm and hand functionProportion of patients with a change in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT)
12 months
Thinking and memoryProportion of patients with reduced number of relapses or freedom from progression of disease
3 months, 6 months and 12 months
Relapses
Who could take part
Relapsing MS · 18 to 60
Show the full criteria
Inclusion criteria
* Males and Females between age 18 and 60 years * Diagnosis of Relapsing Remitting Multiple Sclerosis made by a neurology expert/MS expert with lesions demonstrated on brain MRI that are consistent with MS * Duration of disease: >5 years * Having an EDSS (Kurtzke Expanded Disability Status Scale) score between 3.5 \& 6 * History of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks * Failure to respond or intolerance to the currently available Multiple Sclerosis (MS) immunomodulatory treatments): the lack of response to these treatments will be determined/defined by history of 2 or more relapses within last 2 years with increase in EDSS scale of > 0.5 sustained for > 4 weeks * Must have proof of health insurance in country of residence
Exclusion criteria
* Primary progressive, secondary progressive or progressive relapsing MS as defined by Lublin and Reingold, 1996. These conditions require the presence of continuous clinical disease worsening over a period of at least 3 months. Subjects with these conditions may also have superimposed relapses but are distinguished from relapsing remitting subjects by the lack of clinically stable periods of clinical improvement. * Unable to perform Timed 25-Foot Walk, 9 Hole Peg Test (HPT) (with both upper extremities) and Paced Auditory Serial Addition Test (PASAT 3) * Females who are pregnant or nursing or females of childbearing potential who are unwilling to maintain contraceptive therapy for the duration of the study * Life expectancy \< 6 months due to concomitant illnesses * Exposure to any investigational drug or procedure within 1 month prior to study entry or enrolled in a concurrent study that may confound results of this study. * Active infectious disease: For patients who have tested positive, an expert will be consulted as to patient eligibility based on the patient's infectious status * Any illness which, in the Investigator's judgment, will interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of the study results * Patients on chronic immunosuppressive transplant therapy * Patients with unstable cardiac status (unstable angina, attack of myocardial infarction within last 6 months, uncontrolled high blood pressure, hypotension, cardiomyopathy) * Cerebrovascular accident within 6 months prior to study entry * Patients with poorly controlled diabetes mellitus * Patients with renal insufficiency (Creatinine> 2.5) or failure * Known drug or alcohol dependence or any other factors which will interfere with the study conduct or interpretation of the results or who in the opinion of the investigator is not suitable to participate. * History of cancer (other than non-melanoma skin cancer or in-situ cervical cancer) in the last five years * Unwilling and/or not able to give written informed consent.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
STUDY OBJECTIVES: Primary Objective: Assessment of treatment safety based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post treatment. Secondary objective: Assessment of efficacy at baseline, prior to discharge, 1 month, 3 months, 6 months and 12 months after treatment based on the following: EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29), MS Functional Composite (MSFC) consisting of (1) Timed 25-Foot Walk, (2) 9 Hole Peg Test, and (3) Paced Auditory Serial Addition Test and gadolinium-enhanced magnetic resonance imaging (MRI).
Papers
Results
Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. doi: 10.1001/archneurol.2010.248.Results
Mancardi G, Saccardi R. Autologous haematopoietic stem-cell transplantation in multiple sclerosis. Lancet Neurol. 2008 Jul;7(7):626-36. doi: 10.1016/S1474-4422(08)70138-8.Results
Nash RA, Hutton GJ, Racke MK, Popat U, Devine SM, Griffith LM, Muraro PA, Openshaw H, Sayre PH, Stuve O, Arnold DL, Spychala ME, McConville KC, Harris KM, Phippard D, Georges GE, Wundes A, Kraft GH, Bowen JD. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis (HALT-MS): a 3-year interim report. JAMA Neurol. 2015 Feb;72(2Results
Rice CM, Mallam EA, Whone AL, Walsh P, Brooks DJ, Kane N, Butler SR, Marks DI, Scolding NJ. Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis. Clin Pharmacol Ther. 2010 Jun;87(6):679-85. doi: 10.1038/clpt.2010.44. Epub 2010 May 5.Background
Bermel RA, Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol. 2006 Feb;5(2):158-70. doi: 10.1016/S1474-4422(06)70349-0.Background
Coles A. The curious incident of disability in multiple sclerosis trials. Lancet Neurol. 2006 Nov;5(11):899-900. doi: 10.1016/S1474-4422(06)70585-3. No abstract available.Background
Malgieri A, Kantzari E, Patrizi MP, Gambardella S. Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med. 2010 Sep 7;3(4):248-69.Background
Kurtzke JF. Historical and clinical perspectives of the expanded disability status scale. Neuroepidemiology. 2008;31(1):1-9. doi: 10.1159/000136645. Epub 2008 Jun 6.Background
Rudick R, Antel J, Confavreux C, Cutter G, Ellison G, Fischer J, Lublin F, Miller A, Petkau J, Rao S, Reingold S, Syndulko K, Thompson A, Wallenberg J, Weinshenker B, Willoughby E. Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol. 1997 Sep;42(3):379-82. doi: 10.1002/ana.410420318.Background
Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J, Syndulko K, Weinshenker BG, Antel JP, Confavreux C, Ellison GW, Lublin F, Miller AE, Rao SM, Reingold S, Thompson A, Willoughby E. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999 May;122 ( Pt 5):871-82. doi: 10.1093/brain/122.5.871.
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History
Started
Feb 2015
Main results due
Feb 2017
Finished
Feb 2017