Multiple Sclerosis, Relapsing-RemittingPhase 1TOLERVIT-MSNCT02903537
Tolerogenic Dendritic Cells as a Therapeutic Strategy for the Treatment of Multiple Sclerosis Patients (TOLERVIT-MS)
A Phase 1 study testing Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) and Interferon-beta in people with Multiple Sclerosis, Relapsing-Remitting and Multiple Sclerosis, Chronic Progressive, run by Fundació Institut Germans Trias i Pujol at 2 sites in Spain.
Trial summary
The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive
- What is being tested?
- Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) and Interferon-beta
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesSpain
- Study dates
- 6 Jul 2017to Dec 2023
- Phase
- Phase 1
- 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
- EDSS of 0.0 - 6.5.
- Multiple Sclerosis according to 2010 revised Mc Donald criteria, and less than 15 years of evolution of disease.
- Patients with:
- Active relapsing remitting multiple sclerosis (RRMS) (more than 1 relapse in last year and/or occurrence of ≥3 new T2 lesions or Gd positive) who not wish to be treated with current therapies.
- Low activity RRMS (1 relapse in last year or occurrence of 1 or 2 T2 lesions or Gd positive) without treatment.
- Progressive forms of MS with activity (at least 1 relapse in last year or occurrence 1 or 2 T2 lesions or Gd positive).
Show all 10Show fewer
- RRMS treated with interferon beta (Additional group)
- T cell proliferation to the pool of myelin peptides against which is to induce immune tolerance: Myelin basic protein (MBP)13-32, MBP83-99, MBP111-129, MBP146-170, proteolipid protein (PLP) 139-154, Myelin oligodendrocyte glycoprotein (MOG)1-20, MOG35 -55).
- Adequate peripheral venous access.
- Signed informed consent.
Who cannot join
- Use of corticosteroids during the prior 4 weeks.
- Use of interferon beta -in patients who is retired by inefficiency or other causes- and glatiramer acetate in the 4 weeks prior.
- Use of fingolimod, dimethylfumarate, natalizumab, immunoglobulins or plasmapheresis at 12 weeks; and teriflunomide in the 15 weeks prior.
- Use of azathioprine, mitoxantrone, rituximab, methotrexate, cyclophosphamide, cyclosporine, alemtuzumab or other immunosuppressive drug, except corticosteroids, at any time.
- Bone marrow or stem cell transplant at any time.
- Relapse during the month prior of starting treatment. If it appears and the patient meets the eligibility criteria, must wait long enough until the end of the 30 days free of relapse. If corticosteroids are administered, the MRI performed during this period should not be considered, and a new MRI will be performed at 4 weeks after administration of corticosteroids.
Show all 16Show fewer
- Pregnancy or planning pregnancy within the next 12 months and breastfeeding.
- Fertile patients who are not using an appropriate method of contraception. If the patient is menopausal or sterile it must be documented in the medical record.
- Abusing drugs or alcohol.
- Inability to undergo MRI evaluations.
- Seropositivity for HIV, hepatitis B or C and/or syphilis.
- History of oncological disease.
- Clinically relevant concomitant disease: cardiac, pulmonary, neurological, renal or other major illness.
- Splenectomy.
- Dementia, psychiatric problems or other comorbidities that might interfere protocol compliance.
- To be participating in another clinical study or to have participated in one in the last 3 months.
Trial locations and contacts
2 sites in 1 country.
Spain2 sites, 2 recruiting
- Recruiting
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Cristina Ramo, MD.PhD, +34934978433, cramot.germanstrias@gencat.cat
Ana M Barriocanal, MD.PhD, +34934978488, ambarriocanal@igtp.cat
- Not yet recruiting
Clínica Universidad de Navarra
Pamplona, Navarre, 31008
Jaime Gállego, MD.PhD, +34948255400 ext. 3594, jgallego@unav.es
Amaya Izal, +34948255400 ext. 2724, aizal@unav.es
About this study
Official title: Tolerance-Induction With Dendritic Cells Treated With Vitamin-D3 and Loaded With Myelin Peptides, in Multiple Sclerosis Patients (TOLERVIT-MS)
The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials.
To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.
Read the detailed description
Phase I dose ascending ("best of five") clinical trial.
First group will start by intranodal injection in cervical lymph nodes of 5*10^6 tolDC-VitD3.
Up titration depending on security outcomes to 10*10^6 tolDC-VitD3, same route in second cohort dose and next uptitration to 15*10^6 tolDC-VitD3.
Six cycles per patient with the following schema: for the first four cycles the administration will be each 2 weeks, for the remaining 2 cycles administration each 4 weeks.
A last cohort with the dose identified in the previous groups, administered in patients treated with beta interferon, same route, same dose schema.
- Being tested
- Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3), Interferon-beta
- Keywords
- Multiple Sclerosis, Dendritic Cells, Immune Tolerance, Myelin Proteins, Tolerogenic dendritic cells
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Chronic Progressive, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)Drug
Also called tolDC-VitD3
Intranodal administration
Interferon-betaDrug
Also called beta-interferon
Subcutaneous administration interferon-beta
| Study group | Role | What they receive |
|---|---|---|
| 5 * 10 ^6 tolDC-VitD3 | Experimental | 5 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) Receives: Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) |
| 10 * 10 ^6 tolDC-VitD3 | Experimental | 10 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3). Receives: Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) |
| 15 * 10 ^6 tolDC-VitD3 | Experimental | 15 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3). Receives: Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) |
| Interferon-beta | Experimental | Additional group (patients treated with beta-interferon) will receive the selected dose of those 3 previously cohorts studied Receives: Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3); Drug: Interferon-beta |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by the occurrence and severity of adverse events
Occurence and severity of adverse events will be recorded
Measured: 24 months
Neurologic changes
New relapse. Disability progression on Expanded Disability Status Scale (EDSS)
Measured: 24 months
Radiologic changes
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
Measured: 24 months
Secondary outcomes (9)
Annual relapse rate (ARR)
Measured: 24 months
Expanded Disability Status Scale (EDSS)
Measured: 24 months
9-Hole Peg Test (9HPT)
Measured: 24 months
25-Foot Walking Test (T25FW)
Measured: 24 months
Symbol Digit Modalities Test (SDMT)
Measured: 24 months
Radiologic preliminary efficacy
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
Measured: 24 months
Lymphocyte proliferation to myelin peptides
Measured: 24 months
Blood Immunomonitoring studies
Measured: 24 months
Feasibility
Generation of Good Manufacturing Practices (GMP)-grade cell product released according to Quality Control. Feasibility of cellular product injection.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study start6 Jul 2017
- Primary completionDec 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundació Institut Germans Trias i Pujol
- Sponsor type
- University, hospital or other
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra
- Responsible party
- Sponsor
- Investigators
- Cristina Ramo, MD.PhD.Neurologist, Principal investigator, Badalona Hospital Germans Trias i Pujol. Neurology service. Multiple Sclerosis departmentEva Martínez-Cáceres, MD.PhD.Immunology, Study director, Badalona Hospital Germans Trias i Pujol. Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02903537
- Sponsor's protocol ID
- TOLERVIT-MS
- Other IDs
- 2015-003541-26, 2015
- Acronym
- TOLERVIT-MS
- Status last verified
- Jul 2023
- First submitted
- 21 Jul 2016
- Last updated
- 7 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Lutterotti A, Yousef S, Sputtek A, Sturner KH, Stellmann JP, Breiden P, Reinhardt S, Schulze C, Bester M, Heesen C, Schippling S, Miller SD, Sospedra M, Martin R. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013 Jun 5;5(188):188ra75. doi: 10.1126/scitranslmed.3006168.
PubMed 23740901Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care. 2011 Sep;34(9):2026-32. doi: 10.2337/dc11-0472. Epub 2011 Jun 16.
PubMed 21680720Benham H, Nel HJ, Law SC, Mehdi AM, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, Brunck ME, Hyde C, Trouw LA, Dudek NL, Purcell AW, O'Sullivan BJ, Connolly JE, Paul SK, Le Cao KA, Thomas R. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med. 2015 Jun 3;7(290):290ra87. doi: 10.1126/scitranslmed.aaa9301.
PubMed 26041704Naranjo-Gomez M, Raich-Regue D, Onate C, Grau-Lopez L, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Comparative study of clinical grade human tolerogenic dendritic cells. J Transl Med. 2011 Jun 9;9:89. doi: 10.1186/1479-5876-9-89.
PubMed 21658226Raiotach-Regue D, Grau-Lopez L, Naranjo-Gomez M, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur J Immunol. 2012 Mar;42(3):771-82. doi: 10.1002/eji.201141835.
PubMed 22488365Mansilla MJ, Selles-Moreno C, Fabregas-Puig S, Amoedo J, Navarro-Barriuso J, Teniente-Serra A, Grau-Lopez L, Ramo-Tello C, Martinez-Caceres EM. Beneficial effect of tolerogenic dendritic cells pulsed with MOG autoantigen in experimental autoimmune encephalomyelitis. CNS Neurosci Ther. 2015 Mar;21(3):222-30. doi: 10.1111/cns.12342. Epub 2014 Nov 18.
PubMed 25403984Raich-Regue D, Naranjo-Gomez M, Grau-Lopez L, Ramo C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Differential effects of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. Vaccine. 2012 Jan 5;30(2):378-87. doi: 10.1016/j.vaccine.2011.10.081. Epub 2011 Nov 12.
PubMed 22085546Ten Brinke A, Hilkens CM, Cools N, Geissler EK, Hutchinson JA, Lombardi G, Lord P, Sawitzki B, Trzonkowski P, Van Ham SM, Martinez-Caceres EM. Clinical Use of Tolerogenic Dendritic Cells-Harmonization Approach in European Collaborative Effort. Mediators Inflamm. 2015;2015:471719. doi: 10.1155/2015/471719. Epub 2015 Dec 24.
PubMed 26819498Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, Fouweather T, MacDonald C, Chadwick T, McColl E, Dunn J, Dickinson AM, Hilkens CM, Isaacs JD. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Ann Rheum Dis. 2017 Jan;76(1):227-234. doi: 10.1136/annrheumdis-2015-208456. Epub 2016 Apr 26.
PubMed 27117700Mansilla MJ, Contreras-Cardone R, Navarro-Barriuso J, Cools N, Berneman Z, Ramo-Tello C, Martinez-Caceres EM. Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients. J Neuroinflammation. 2016 May 20;13(1):113. doi: 10.1186/s12974-016-0584-9.
PubMed 27207486Willekens B, Presas-Rodriguez S, Mansilla MJ, Derdelinckx J, Lee WP, Nijs G, De Laere M, Wens I, Cras P, Parizel P, Van Hecke W, Ribbens A, Billiet T, Adams G, Couttenye MM, Navarro-Barriuso J, Teniente-Serra A, Quirant-Sanchez B, Lopez-Diaz de Cerio A, Inoges S, Prosper F, Kip A, Verheij H, Gross CC, Wiendl H, Van Ham MS, Ten Brinke A, Barriocanal AM, Massuet-Vilamajo A, Hens N, Berneman Z, Martinez-Caceres E, Cools N, Ramo-Tello C; RESTORE consortium. Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration. BMJ Open. 2019 Sep 9;9(9):e030309. doi: 10.1136/bmjopen-2019-030309.
PubMed 31501122
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolerance-Induction With Dendritic Cells Treated With Vitamin-D3 and Loaded With Myelin Peptides, in Multiple Sclerosis Patients (TOLERVIT-MS)
- ClinicalTrials.gov ID
- NCT02903537
- Acronym / sponsor ID
- TOLERVIT-MS / TOLERVIT-MS
- Keywords
- Multiple Sclerosis, Dendritic Cells, Immune Tolerance, Myelin Proteins, Tolerogenic dendritic cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Fundació Institut Germans Trias i PujolUniversity, hospital or other
- Collaborators
- Clinica Universidad de Navarra, Universidad de Navarra
- Study start
- 6 Jul 2017 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 16 Sep 2016 (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.
The purpose of this study is to determine the safety and tolerability of the intranodal administration of autologous monocyte-derived dendritic cells tolerised with Vitamin-D3 and pulsed with myelin peptides (tolDC-VitD3) in multiple sclerosis patients . To select the most appropriate regime for the development of future therapeutic trials.
To evaluate the preliminary proof of concept by clinical and/or radiological activity and immunological markers.
Detailed description
Phase I dose ascending ("best of five") clinical trial.
First group will start by intranodal injection in cervical lymph nodes of 5*10^6 tolDC-VitD3.
Up titration depending on security outcomes to 10*10^6 tolDC-VitD3, same route in second cohort dose and next uptitration to 15*10^6 tolDC-VitD3.
Six cycles per patient with the following schema: for the first four cycles the administration will be each 2 weeks, for the remaining 2 cycles administration each 4 weeks.
A last cohort with the dose identified in the previous groups, administered in patients treated with beta interferon, same route, same dose schema.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 5 * 10 ^6 tolDC-VitD3 | Experimental | Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)5 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) |
| 10 * 10 ^6 tolDC-VitD3 | Experimental | Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)10 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3). |
| 15 * 10 ^6 tolDC-VitD3 | Experimental | Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)15 million autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3). |
| Interferon-beta | Experimental | Drug: Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3), Drug: Interferon-betaAdditional group (patients treated with beta-interferon) will receive the selected dose of those 3 previously cohorts studied |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- EDSS of 0.0 - 6.5.
- Multiple Sclerosis according to 2010 revised Mc Donald criteria, and less than 15 years of evolution of disease.
- Patients with:
- T cell proliferation to the pool of myelin peptides against which is to induce immune tolerance: Myelin basic protein (MBP)13-32, MBP83-99, MBP111-129, MBP146-170, proteolipid protein (PLP) 139-154, Myelin oligodendrocyte glycoprotein (MOG)1-20, MOG35 -55).
- Adequate peripheral venous access.
Key exclusion criteria (16 listed)
- Use of corticosteroids during the prior 4 weeks.
- Use of interferon beta -in patients who is retired by inefficiency or other causes- and glatiramer acetate in the 4 weeks prior.
- Use of fingolimod, dimethylfumarate, natalizumab, immunoglobulins or plasmapheresis at 12 weeks; and teriflunomide in the 15 weeks prior.
- Use of azathioprine, mitoxantrone, rituximab, methotrexate, cyclophosphamide, cyclosporine, alemtuzumab or other immunosuppressive drug, except corticosteroids, at any time.
- Bone marrow or stem cell transplant at any time.
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 VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3)Also: tolDC-VitD3Intranodal administration | Drug | 10 * 10 ^6 tolDC-VitD3, 15 * 10 ^6 tolDC-VitD3, 5 * 10 ^6 tolDC-VitD3, Interferon-beta |
| Interferon-betaAlso: beta-interferonSubcutaneous administration interferon-beta | Drug | Interferon-beta |
Primary outcome
Safety as assessed by the occurrence and severity of adverse events
Time frame: 24 months
Occurence and severity of adverse events will be recorded
Neurologic changes
Time frame: 24 months
New relapse. Disability progression on Expanded Disability Status Scale (EDSS)
Radiologic changes
Time frame: 24 months
Number of new or enlarging T2 lesions on brain MRI. Number of Gadolinium (Gd)-enhancing T1 lesions on brain MRI
9 secondary outcomes
Annual relapse rate (ARR)
Time frame: 24 months
Expanded Disability Status Scale (EDSS)
Time frame: 24 months
9-Hole Peg Test (9HPT)
Time frame: 24 months
25-Foot Walking Test (T25FW)
Time frame: 24 months
Symbol Digit Modalities Test (SDMT)
Time frame: 24 months
Radiologic preliminary efficacy
Time frame: 24 months
Lymphocyte proliferation to myelin peptides
Time frame: 24 months
Blood Immunomonitoring studies
Time frame: 24 months
Feasibility
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Background: PubMed 23740901Lutterotti A, Yousef S, Sputtek A, Sturner KH, Stellmann JP, Breiden P, Reinhardt S, Schulze C, Bester M, Heesen C, Schippling S, Miller SD, Sospedra M, Martin R. Antigen-specific tolerance by autologous myelin peptide-coupled cells: a phase 1 trial in multiple sclerosis. Sci Transl Med. 2013 Jun 5;5(188):188ra75. doi: 10.1126/scitranslmed.3006168.
- Background: PubMed 21680720Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care. 2011 Sep;34(9):2026-32. doi: 10.2337/dc11-0472. Epub 2011 Jun 16.
- Background: PubMed 26041704Benham H, Nel HJ, Law SC, Mehdi AM, Street S, Ramnoruth N, Pahau H, Lee BT, Ng J, Brunck ME, Hyde C, Trouw LA, Dudek NL, Purcell AW, O'Sullivan BJ, Connolly JE, Paul SK, Le Cao KA, Thomas R. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med. 2015 Jun 3;7(290):290ra87. doi: 10.1126/scitranslmed.aaa9301.
- Background: PubMed 21658226Naranjo-Gomez M, Raich-Regue D, Onate C, Grau-Lopez L, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Comparative study of clinical grade human tolerogenic dendritic cells. J Transl Med. 2011 Jun 9;9:89. doi: 10.1186/1479-5876-9-89.
- Background: PubMed 22488365Raiotach-Regue D, Grau-Lopez L, Naranjo-Gomez M, Ramo-Tello C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur J Immunol. 2012 Mar;42(3):771-82. doi: 10.1002/eji.201141835.
- Background: PubMed 25403984Mansilla MJ, Selles-Moreno C, Fabregas-Puig S, Amoedo J, Navarro-Barriuso J, Teniente-Serra A, Grau-Lopez L, Ramo-Tello C, Martinez-Caceres EM. Beneficial effect of tolerogenic dendritic cells pulsed with MOG autoantigen in experimental autoimmune encephalomyelitis. CNS Neurosci Ther. 2015 Mar;21(3):222-30. doi: 10.1111/cns.12342. Epub 2014 Nov 18.
- Background: PubMed 22085546Raich-Regue D, Naranjo-Gomez M, Grau-Lopez L, Ramo C, Pujol-Borrell R, Martinez-Caceres E, Borras FE. Differential effects of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. Vaccine. 2012 Jan 5;30(2):378-87. doi: 10.1016/j.vaccine.2011.10.081. Epub 2011 Nov 12.
- Background: PubMed 26819498Ten Brinke A, Hilkens CM, Cools N, Geissler EK, Hutchinson JA, Lombardi G, Lord P, Sawitzki B, Trzonkowski P, Van Ham SM, Martinez-Caceres EM. Clinical Use of Tolerogenic Dendritic Cells-Harmonization Approach in European Collaborative Effort. Mediators Inflamm. 2015;2015:471719. doi: 10.1155/2015/471719. Epub 2015 Dec 24.
- Background: PubMed 27117700Bell GM, Anderson AE, Diboll J, Reece R, Eltherington O, Harry RA, Fouweather T, MacDonald C, Chadwick T, McColl E, Dunn J, Dickinson AM, Hilkens CM, Isaacs JD. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Ann Rheum Dis. 2017 Jan;76(1):227-234. doi: 10.1136/annrheumdis-2015-208456. Epub 2016 Apr 26.
- Background: PubMed 27207486Mansilla MJ, Contreras-Cardone R, Navarro-Barriuso J, Cools N, Berneman Z, Ramo-Tello C, Martinez-Caceres EM. Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients. J Neuroinflammation. 2016 May 20;13(1):113. doi: 10.1186/s12974-016-0584-9.
- Derived from this study: PubMed 31501122Willekens B, Presas-Rodriguez S, Mansilla MJ, Derdelinckx J, Lee WP, Nijs G, De Laere M, Wens I, Cras P, Parizel P, Van Hecke W, Ribbens A, Billiet T, Adams G, Couttenye MM, Navarro-Barriuso J, Teniente-Serra A, Quirant-Sanchez B, Lopez-Diaz de Cerio A, Inoges S, Prosper F, Kip A, Verheij H, Gross CC, Wiendl H, Van Ham MS, Ten Brinke A, Barriocanal AM, Massuet-Vilamajo A, Hens N, Berneman Z, Martinez-Caceres E, Cools N, Ramo-Tello C; RESTORE consortium. Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration. BMJ Open. 2019 Sep 9;9(9):e030309. doi: 10.1136/bmjopen-2019-030309.
- European Cooperation in Science and Technology (COST), Action BM1305 "Action to focus and accelerate cell-based tolerogenic therapies"Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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.
Cristina Ramo, MD.PhD.Neurologist principal investigator
Badalona Hospital Germans Trias i Pujol. Neurology service. Multiple Sclerosis department
Eva Martínez-Cáceres, MD.PhD.Immunology study director
Badalona Hospital Germans Trias i Pujol. Immunology
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous VitD3 tolerogenic monocyte-derived dendritic cells loaded with a pool of myelin peptides (tolDC-VitD3) and Interferon-beta in people with Multiple Sclerosis, Relapsing-Remitting and Multiple Sclerosis, Chronic Progressive, run by Fundació Institut Germans Trias i Pujol at 2 sites in Spain.
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 10 inclusion and 16 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 7 Jul 2023. 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 Spain. 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 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.
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 Cristina Ramo, MD.PhD. Neurologist (+34934978433, cramot.germanstrias@gencat.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as assessed by the occurrence and severity of adverse events (time frame: 24 months). The study lists 3 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 NCT02903537, which also lists 11 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 7 Jul 2023.