Multiple Sclerosis, Relapsing-RemittingPhase 1/2NCT02418325
A Study of Allogeneic Human UC-MSC and Liberation Therapy (When Associated With CCSVI) in Patients With RRMS
A Phase 1/2 study testing Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells and Liberation therapy in people with Multiple Sclerosis, Relapsing-Remitting, run by Genesis Limited at 1 site in Trinidad and Tobago.
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?
- Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal 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
- 1 siteTrinidad and Tobago
- 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
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- 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
1 site in 1 country.
Trinidad and Tobago1 site
Genesis Institute of Cellular Medicine, Genesis (Trinidad and Tobago) Private Limited
San Fernando, Trinidad
About this study
Official title: An Open-label, Non-randomized, Phase I/II Study of Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and Liberation Therapy (When Associated With Chronic Cerebrovascular Venous Insufficiency) in Patients With Relapsing Remitting Multiple Sclerosis (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: Wharton Jelly derived allogeneic MSCs.
Method of administration and dose: Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs 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 allogeneic umbilical cord mesenchymal stem cells (UC-MSC) 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 than 0.5 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 endpoint 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 timepoint. 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
- Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal 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.
Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem CellsBiological
Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs in dose of 100 million along with liberation therapy (when associated with CCSVI)
Liberation therapyOther
| Study group | Role | What they receive |
|---|---|---|
| AllogeneicHumanUmbilicalCordTissue-DerivedMesenchymalStemCells | Experimental | Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs in dose of 100 million along with liberation therapy (when associated with CCSVI) Receives: Biological: Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal 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
Proportion of patients with clinical improvement in EDSS score compared to baseline (Time Frame: 12 months). Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
Measured: Up to 12 months
Secondary outcomes (10)
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 clinical improvement in MSFC 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 posted16 Apr 2015 (estimated)
- Study startFeb 2015
- Primary completionFeb 2017 (estimated)
- Study completionFeb 2017 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (29)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
- Genesis Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dr. Bill Brashier, M.D, Principal investigator, Genesis Institute of Cellular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418325
- Sponsor's protocol ID
- PRT/GENESIS/2015/001
- Status last verified
- Nov 2015
- First submitted
- 8 Apr 2015
- Last updated
- 4 Nov 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 17052654Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol. 2000 Dec;48(6):893-901.
PubMed 11117546Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol. 2014 Jan;75(1):43-9. doi: 10.1002/ana.24018. Epub 2014 Jan 2.
PubMed 24006277Till C, Ghassemi R, Aubert-Broche B, Kerbrat A, Collins DL, Narayanan S, Arnold DL, Desrocher M, Sled JG, Banwell BL. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology. 2011 May;25(3):319-32. doi: 10.1037/a0022051.
PubMed 21534686Yaldizli O, Penner IK, Frontzek K, Naegelin Y, Amann M, Papadopoulou A, Sprenger T, Kuhle J, Calabrese P, Radu EW, Kappos L, Gass A. The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients. Mult Scler. 2014 Mar;20(3):356-64. doi: 10.1177/1352458513496880. Epub 2013 Aug 19.
PubMed 23959709Rudick RA, Lee JC, Nakamura K, Fisher E. Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci. 2009 Jul 15;282(1-2):106-11. doi: 10.1016/j.jns.2008.11.018. Epub 2008 Dec 19.
PubMed 19100997Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009 May;5(5):256-66. doi: 10.1038/nrneurol.2009.41.
PubMed 19488083Popescu 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 23524331Pugliatti M, Rosati G, Carton H, Riise T, Drulovic J, Vecsei L, Milanov I. The epidemiology of multiple sclerosis in Europe. Eur J Neurol. 2006 Jul;13(7):700-22. doi: 10.1111/j.1468-1331.2006.01342.x.
PubMed 16834700Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringden O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X.
PubMed 18468541Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004 May 1;363(9419):1439-41. doi: 10.1016/S0140-6736(04)16104-7.
PubMed 15121408Kurtzke 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 10355672
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 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 Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and Liberation Therapy (When Associated With Chronic Cerebrovascular Venous Insufficiency) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)
- ClinicalTrials.gov ID
- NCT02418325
- Acronym / sponsor ID
- PRT/GENESIS/2015/001
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- RRMS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 69 participants (estimated)
- Lead sponsor
- Genesis LimitedIndustry (pharma, biotech, devices)
- Study start
- Feb 2015
- Primary completion
- Feb 2017 (estimated)
- Study completion
- Feb 2017 (estimated)
- First posted
- 16 Apr 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: Wharton Jelly derived allogeneic MSCs.
Method of administration and dose: Super selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs 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 allogeneic umbilical cord mesenchymal stem cells (UC-MSC) 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 than 0.5 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 endpoint 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 timepoint. 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 |
|---|---|---|
| AllogeneicHumanUmbilicalCordTissue-DerivedMesenchymalStemCells | Experimental | Biological: Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells, Other: Liberation therapySuper selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs 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 |
|---|---|---|
| Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem CellsSuper selective intravenous administration of 50 million Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells (UC-MSC) and intrathecal administration of UC-MSCs in dose of 100 million along with liberation therapy (when associated with CCSVI) | Biological | AllogeneicHumanUmbilicalCordTissue-DerivedMesenchymalStemCells |
| Liberation therapy | Other | AllogeneicHumanUmbilicalCordTissue-DerivedMesenchymalStemCells |
Primary outcome
Proportion of patients with clinical improvement in EDSS score compared to baseline
Time frame: Up to 12 months
Proportion of patients with clinical improvement in EDSS score compared to baseline (Time Frame: 12 months). Clinical improvement is defined as decrease in Expanded Disability Status Scale (EDSS) score greater than 0.5 from baseline.
10 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 clinical improvement in MSFC 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
The study was stopped early (reason given: Lack of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 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 11117546Bjartmar C, Kidd G, Mork S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol. 2000 Dec;48(6):893-901.
- Background: PubMed 24006277Sormani MP, Arnold DL, De Stefano N. Treatment effect on brain atrophy correlates with treatment effect on disability in multiple sclerosis. Ann Neurol. 2014 Jan;75(1):43-9. doi: 10.1002/ana.24018. Epub 2014 Jan 2.
- Background: PubMed 21534686Till C, Ghassemi R, Aubert-Broche B, Kerbrat A, Collins DL, Narayanan S, Arnold DL, Desrocher M, Sled JG, Banwell BL. MRI correlates of cognitive impairment in childhood-onset multiple sclerosis. Neuropsychology. 2011 May;25(3):319-32. doi: 10.1037/a0022051.
- Background: PubMed 23959709Yaldizli O, Penner IK, Frontzek K, Naegelin Y, Amann M, Papadopoulou A, Sprenger T, Kuhle J, Calabrese P, Radu EW, Kappos L, Gass A. The relationship between total and regional corpus callosum atrophy, cognitive impairment and fatigue in multiple sclerosis patients. Mult Scler. 2014 Mar;20(3):356-64. doi: 10.1177/1352458513496880. Epub 2013 Aug 19.
- Background: PubMed 19100997Rudick RA, Lee JC, Nakamura K, Fisher E. Gray matter atrophy correlates with MS disability progression measured with MSFC but not EDSS. J Neurol Sci. 2009 Jul 15;282(1-2):106-11. doi: 10.1016/j.jns.2008.11.018. Epub 2008 Dec 19.
- Background: PubMed 19488083Barkhof F, Calabresi PA, Miller DH, Reingold SC. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009 May;5(5):256-66. doi: 10.1038/nrneurol.2009.41.
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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
Genesis Institute of Cellular Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Allogeneic Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells and Liberation therapy in people with Multiple Sclerosis, Relapsing-Remitting, run by Genesis Limited at 1 site in Trinidad and Tobago.
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: stopped early, as of the sponsor's last update on 4 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
The study was stopped early (reason given: Lack of funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. 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). 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 NCT02418325, which also lists 29 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 4 Nov 2015.