Multiple Sclerosis, Relapsing-RemittingPhase 1/2NCT02587806
A Study of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and Liberation Therapy (When Associated With CCSVI) in Patients With RRMS
A Phase 1/2 study testing Autologous Bone Marrow-Derived Mononuclear Stem Cells and Liberation therapy in people with Multiple Sclerosis, Relapsing-Remitting, run by Novo Cellular Medicine Institute LLP at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Autologous Bone Marrow-Derived Mononuclear Stem Cells and Liberation therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 69 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Feb 2015to Feb 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
India1 site, 1 recruiting
- Recruiting
Inamdar Multispecialty Hospital
Pune, Maharashtra, 411040
Dr. Malik Javeri, M.D., +91 9766476793, india@novomedinstitute.org
Dr. Malik Javeri, M.D.
Trinidad and Tobago1 site, 1 recruiting
- Recruiting
Novo Cellular Medicine Institute
San Fernando, Trinidad
Dr. Bill Brashier, M.D., 001868 770 9152, drbill@novomedinstitute.org
Dr. Bill Brashier, M.D.
About this study
Official title: 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
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).
Read the detailed description
STUDY TREATMENT:
Investigational therapy product: Autologous Bone Marrow-Derived Mesenchymal Stem Cells (BM-MNC).
Method of administration and dose: Super selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI).
SAFETY AND EFFICACY EVALUATION:
The proposed study will assess safety and primary and secondary efficacy endpoints after super selective intravenous and intrathecal administration of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) in 69 patients with Relapsing Remitting Multiple Sclerosis.
Safety Evaluation:
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.
Efficacy evaluation:
Clinical evaluations, including EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29) will be performed at baseline before stem cell mobilization, prior to discharge at 1, 3, 6 and 12 months after stem cell therapy.
The MS Functional Composite (MSFC) consists of the (a) Timed 25-Foot Walk, (b) 9 Hole Peg Test, and (c) Paced Auditory Serial Addition Test will be performed at baseline before stem cell mobilization and at 12 months after stem cell therapy.
Gadolinium enhanced MRI scans of the brain will be performed at baseline before therapy and then 12 months after stem cell therapy. Follow-up scans will be performed on the same type of scanner used at baseline. Scans will be analyzed centrally. The 'baseline MRI scan' will be the reference for brain volume changes.
DATA COLLECTION AND STATISTICAL ANALYSIS:
Descriptive analyses of the adverse events will be performed. Proportion of adverse events at each visit will be calculated using frequency distribution. The frequency, severity, timing and the potential relationship to the intervention will be assessed in order to characterize the safety of the intervention.
The probability of overall event-free survival (as well as progression-free, relapse-free, or MRI event-free survival) at baseline through 1 year will be calculated. The end point of progression is defined as increased Expanded Disability Status Scale (EDSS) score greater than0.5 from baseline. Analyses will be conducted using Kaplan- Meier estimates with Wald-type 90% CIs based on Greenwood's formula for SE.
Descriptive analyses of all primary and secondary efficacy endpoints will be performed using descriptive statistics. Proportion of patients with clinically significant change in this efficacy measurement scales (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC- Nine Hole Peg Test, MSFC- Paced Auditory Serial Addition Test) and change in gadolinium enhancing lesions, new T2 lesions from previous visit will be presented as a proportion.
The percentage of change in brain volume will be calculated from screening and analyzed by end point status at month 12 with an exact Wilcoxon rank sum test using mean scores when the results are identical.The null hypothesis tests whether the median percentage of change in brain volume among participants who met the end point by month 12 is equal to the median of those who have not met the end point by month 12.
Other primary and secondary efficacy endpoints (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC- Nine Hole Peg Test, MSFC- Paced Auditory Serial Addition Test) will be analyzed using a Wilcoxon signed rank test.Change from baseline outcomes for all the endpoints will be calculated for each patient who underwent stem cell transplant as the post transplant value minus the baseline value. The null hypothesis tests whether the median difference from baseline measurement in the values at the month 1, month 3, month 6 and month 12 visits was significantly different from zero,with baseline measurement defined as the screening assessment for the percentage of change in brain volume and the baseline visit for all other end points.
To calculate MSFC, results from each of the 3 components will be transformed into a z score and averaged to yield a composite for each patient at each time point. The z scores that compose the MSFC score will be calculated using the reference population from the National Multiple Sclerosis Society Task Force database.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Autologous Bone Marrow-Derived Mononuclear Stem Cells, Liberation therapy
- Keywords
- RRMS
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Bone Marrow-Derived Mononuclear Stem CellsBiological
Super selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI)
Liberation therapyOther
| Study group | Role | What they receive |
|---|---|---|
| Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) | Experimental | Super selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI) Receives: Biological: Autologous Bone Marrow-Derived Mononuclear Stem Cells; Other: Liberation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with clinical improvement in EDSS score compared to baseline
Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
Measured: Up to 12 months
Proportion of patients with adverse events
Measured: up to 12 months
Secondary outcomes (9)
Proportion of patients with a change in either gadolinium enhancing or new T2-weighted lesions on brain MRI
Measured: 12 months
Proportion of patients with reduction in T2 lesion volume on brain MRI
Measured: 12 months
Proportion of patients with reduction in brain volume on MRI
Measured: 12 months
Proportion of patients with clinical improvement in EDSS score compared to baseline
Measured: 3 months and 6 months
Proportion of patients with clinical improvement in MSIS score compared to baseline
Measured: 3 months, 6 months and 12 months
Proportion of patients with a change in mobility and leg function as measured by the 25 foot walking test
Measured: 12 months
Proportion of patients with a change in upper extremity function as measured by the Nine Hole Peg Test
Measured: 12 months
Proportion of patients with a change in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT)
Measured: 12 months
Proportion of patients with reduced number of relapses or freedom from progression of disease
Measured: 3 months, 6 months and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2015 (estimated)
- Study startFeb 2015
- Primary completionFeb 2017 (estimated)
- Study completionFeb 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 69 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Novo Cellular Medicine Institute LLP
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Bill Brashier, M.D., Principal investigator, Novo Cellular Medicine Institute LLP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02587806
- Sponsor's protocol ID
- PRT/NOVO/2015/002
- Status last verified
- Oct 2015
- First submitted
- 26 Oct 2015
- Last updated
- 28 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 16426992Coles 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.
PubMed 17052654Malgieri 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.
PubMed 21072260Kurtzke 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.
PubMed 18535394Rudick 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.
PubMed 9307263Cutter 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.
PubMed 10355672Bonzano L, Roccatagliata L, Mancardi GL, Sormani MP. Gadolinium-enhancing or active T2 magnetic resonance imaging lesions in multiple sclerosis clinical trials? Mult Scler. 2009 Sep;15(9):1043-7. doi: 10.1177/1352458509106610. Epub 2009 Jul 1.
PubMed 19570818Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002 Jan 17;346(3):158-64. doi: 10.1056/NEJMoa011341.
PubMed 11796849O'Riordan JI, Gawne Cain M, Coles A, Wang L, Compston DA, Tofts P, Miller DH. T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation. Mult Scler. 1998 Oct;4(5):408-12. doi: 10.1177/135245859800400502.
PubMed 9839300Chitnis T, Tardieu M, Amato MP, Banwell B, Bar-Or A, Ghezzi A, Kornberg A, Krupp LB, Pohl D, Rostasy K, Tenembaum S, Waubant E, Wassmer E. International Pediatric MS Study Group Clinical Trials Summit: meeting report. Neurology. 2013 Mar 19;80(12):1161-8. doi: 10.1212/WNL.0b013e318288694e.
PubMed 23509048Sormani MP, Bonzano L, Roccatagliata L, Cutter GR, Mancardi GL, Bruzzi P. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol. 2009 Mar;65(3):268-75. doi: 10.1002/ana.21606.
PubMed 19334061Sormani MP, Stubinski B, Cornelisse P, Rocak S, Li D, De Stefano N. Magnetic resonance active lesions as individual-level surrogate for relapses in multiple sclerosis. Mult Scler. 2011 May;17(5):541-9. doi: 10.1177/1352458510391837. Epub 2010 Dec 9.
PubMed 21148262Sormani MP, Bruzzi P, Beckmann K, Wagner K, Miller DH, Kappos L, Filippi M; European Study Group on Interferon Beta-1b in Secondary Progressive MS. MRI metrics as surrogate endpoints for EDSS progression in SPMS patients treated with IFN beta-1b. Neurology. 2003 May 13;60(9):1462-6. doi: 10.1212/01.wnl.0000063312.15758.b3.
PubMed 12743232Pascual AM, Martinez-Bisbal MC, Bosca I, Valero C, Coret F, Martinez-Granados B, Marti-Bonmati L, Mir A, Celda B, Casanova B. Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis. Neurology. 2007 Jul 3;69(1):63-7. doi: 10.1212/01.wnl.0000265054.08610.12.
PubMed 17606882Popescu V, Agosta F, Hulst HE, Sluimer IC, Knol DL, Sormani MP, Enzinger C, Ropele S, Alonso J, Sastre-Garriga J, Rovira A, Montalban X, Bodini B, Ciccarelli O, Khaleeli Z, Chard DT, Matthews L, Palace J, Giorgio A, De Stefano N, Eisele P, Gass A, Polman CH, Uitdehaag BM, Messina MJ, Comi G, Filippi M, Barkhof F, Vrenken H; MAGNIMS Study Group. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1082-91. doi: 10.1136/jnnp-2012-304094. Epub 2013 Mar 23.
PubMed 23524331
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02587806
- Acronym / sponsor ID
- PRT/NOVO/2015/002
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- RRMS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- Novo Cellular Medicine Institute LLPIndustry (pharma, biotech, devices)
- Study start
- Feb 2015
- Primary completion
- Feb 2017 (estimated)
- Study completion
- Feb 2017 (estimated)
- First posted
- 27 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
STUDY TREATMENT:
Investigational therapy product: Autologous Bone Marrow-Derived Mesenchymal Stem Cells (BM-MNC).
Method of administration and dose: Super selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI).
SAFETY AND EFFICACY EVALUATION:
The proposed study will assess safety and primary and secondary efficacy endpoints after super selective intravenous and intrathecal administration of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) in 69 patients with Relapsing Remitting Multiple Sclerosis.
Safety Evaluation:
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.
Efficacy evaluation:
Clinical evaluations, including EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29) will be performed at baseline before stem cell mobilization, prior to discharge at 1, 3, 6 and 12 months after stem cell therapy.
The MS Functional Composite (MSFC) consists of the (a) Timed 25-Foot Walk, (b) 9 Hole Peg Test, and (c) Paced Auditory Serial Addition Test will be performed at baseline before stem cell mobilization and at 12 months after stem cell therapy.
Gadolinium enhanced MRI scans of the brain will be performed at baseline before therapy and then 12 months after stem cell therapy. Follow-up scans will be performed on the same type of scanner used at baseline. Scans will be analyzed centrally. The 'baseline MRI scan' will be the reference for brain volume changes.
DATA COLLECTION AND STATISTICAL ANALYSIS:
Descriptive analyses of the adverse events will be performed. Proportion of adverse events at each visit will be calculated using frequency distribution. The frequency, severity, timing and the potential relationship to the intervention will be assessed in order to characterize the safety of the intervention.
The probability of overall event-free survival (as well as progression-free, relapse-free, or MRI event-free survival) at baseline through 1 year will be calculated. The end point of progression is defined as increased Expanded Disability Status Scale (EDSS) score greater than0.5 from baseline. Analyses will be conducted using Kaplan- Meier estimates with Wald-type 90% CIs based on Greenwood's formula for SE.
Descriptive analyses of all primary and secondary efficacy endpoints will be performed using descriptive statistics. Proportion of patients with clinically significant change in this efficacy measurement scales (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC- Nine Hole Peg Test, MSFC- Paced Auditory Serial Addition Test) and change in gadolinium enhancing lesions, new T2 lesions from previous visit will be presented as a proportion.
The percentage of change in brain volume will be calculated from screening and analyzed by end point status at month 12 with an exact Wilcoxon rank sum test using mean scores when the results are identical.The null hypothesis tests whether the median percentage of change in brain volume among participants who met the end point by month 12 is equal to the median of those who have not met the end point by month 12.
Other primary and secondary efficacy endpoints (EDSS, MSIS, MSFC, MSFC-25 foot walking test, MSFC- Nine Hole Peg Test, MSFC- Paced Auditory Serial Addition Test) will be analyzed using a Wilcoxon signed rank test.Change from baseline outcomes for all the endpoints will be calculated for each patient who underwent stem cell transplant as the post transplant value minus the baseline value. The null hypothesis tests whether the median difference from baseline measurement in the values at the month 1, month 3, month 6 and month 12 visits was significantly different from zero,with baseline measurement defined as the screening assessment for the percentage of change in brain volume and the baseline visit for all other end points.
To calculate MSFC, results from each of the 3 components will be transformed into a z score and averaged to yield a composite for each patient at each time point. The z scores that compose the MSFC score will be calculated using the reference population from the National Multiple Sclerosis Society Task Force database.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) | Experimental | Biological: Autologous Bone Marrow-Derived Mononuclear Stem Cells, Other: Liberation therapySuper selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Bone Marrow-Derived Mononuclear Stem CellsSuper selective intravenous administration of 50 million Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and intrathecal administration of BM-MNCs in dose of 100 million along with liberation therapy (when associated with CCSVI) | Biological | Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) |
| Liberation therapy | Other | Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) |
Primary outcome
Proportion of patients with clinical improvement in EDSS score compared to baseline
Time frame: Up to 12 months
Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
Proportion of patients with adverse events
Time frame: up to 12 months
9 secondary outcomes
Proportion of patients with a change in either gadolinium enhancing or new T2-weighted lesions on brain MRI
Time frame: 12 months
Proportion of patients with reduction in T2 lesion volume on brain MRI
Time frame: 12 months
Proportion of patients with reduction in brain volume on MRI
Time frame: 12 months
Proportion of patients with clinical improvement in EDSS score compared to baseline
Time frame: 3 months and 6 months
Proportion of patients with clinical improvement in MSIS score compared to baseline
Time frame: 3 months, 6 months and 12 months
Proportion of patients with a change in mobility and leg function as measured by the 25 foot walking test
Time frame: 12 months
Proportion of patients with a change in upper extremity function as measured by the Nine Hole Peg Test
Time frame: 12 months
Proportion of patients with a change in cognitive function as measured by the Paced Auditory Serial Addition Test (PASAT)
Time frame: 12 months
Proportion of patients with reduced number of relapses or freedom from progression of disease
Time frame: 3 months, 6 months and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2015.
- Background: PubMed 16426992Bermel 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: PubMed 17052654Coles 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: PubMed 21072260Malgieri 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: PubMed 18535394Kurtzke 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: PubMed 9307263Rudick 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: PubMed 10355672Cutter 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.
- Background: PubMed 19570818Bonzano L, Roccatagliata L, Mancardi GL, Sormani MP. Gadolinium-enhancing or active T2 magnetic resonance imaging lesions in multiple sclerosis clinical trials? Mult Scler. 2009 Sep;15(9):1043-7. doi: 10.1177/1352458509106610. Epub 2009 Jul 1.
- Background: PubMed 11796849Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002 Jan 17;346(3):158-64. doi: 10.1056/NEJMoa011341.
- Background: PubMed 9839300O'Riordan JI, Gawne Cain M, Coles A, Wang L, Compston DA, Tofts P, Miller DH. T1 hypointense lesion load in secondary progressive multiple sclerosis: a comparison of pre versus post contrast loads and of manual versus semi automated threshold techniques for lesion segmentation. Mult Scler. 1998 Oct;4(5):408-12. doi: 10.1177/135245859800400502.
- Background: PubMed 23509048Chitnis T, Tardieu M, Amato MP, Banwell B, Bar-Or A, Ghezzi A, Kornberg A, Krupp LB, Pohl D, Rostasy K, Tenembaum S, Waubant E, Wassmer E. International Pediatric MS Study Group Clinical Trials Summit: meeting report. Neurology. 2013 Mar 19;80(12):1161-8. doi: 10.1212/WNL.0b013e318288694e.
- Background: PubMed 19334061Sormani MP, Bonzano L, Roccatagliata L, Cutter GR, Mancardi GL, Bruzzi P. Magnetic resonance imaging as a potential surrogate for relapses in multiple sclerosis: a meta-analytic approach. Ann Neurol. 2009 Mar;65(3):268-75. doi: 10.1002/ana.21606.
- Background: PubMed 21148262Sormani MP, Stubinski B, Cornelisse P, Rocak S, Li D, De Stefano N. Magnetic resonance active lesions as individual-level surrogate for relapses in multiple sclerosis. Mult Scler. 2011 May;17(5):541-9. doi: 10.1177/1352458510391837. Epub 2010 Dec 9.
Related trials for Multiple Sclerosis, Relapsing-Remitting
Active, not recruiting
Myrosinase Bioactivated Gglucoraphanin for the Treatment of Neurodegenerative Diseases (GRA-MYR-ND)
PARKINSON DISEASE (Disorder), Multiple Sclerosis (MS) - Relapsing-remitting
Recruiting
Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study
Multiple Sclerosis (MS) - Relapsing-remitting, Upper Extremity Dysfunction
Not yet recruiting
Treatment of Memory Retrieval Impairments in MS With HDtDCS to the LIFG in a Placebo Controlled Trial
Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis (RRMS)
Recruiting
Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity
Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Bill Brashier, M.D. principal investigator
Novo Cellular Medicine Institute LLP
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous Bone Marrow-Derived Mononuclear Stem Cells and Liberation therapy in people with Multiple Sclerosis, Relapsing-Remitting, run by Novo Cellular Medicine Institute LLP at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in India, Trinidad and Tobago. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dr. Senthil Thyagarajan, PhD (+91 8554982236, drsenthil@novomedinstitute.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with clinical improvement in EDSS score compared to baseline (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02587806, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2015.