Progressive Multiple Sclerosis Clinical Trial
— ACTiMuSOfficial title:
Assessment of Bone Marrow-derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS)
Multiple sclerosis - MS - affects 1.3m people worldwide, costing the European Union economy
€9 billion/year, through both direct and indirect consequences of progressive disability.
Despite the usual relapsing-remitting presentation, over 80% of patients develop progressive
disability; 40% require a wheelchair within 10 years of diagnosis. At present, there are no
treatments that reverse, halt or even slow progressive disability in MS.
The investigators recently completed one of the first feasibility/safety trials in the world
of reparative bone marrow cell therapy in 6 patients with longstanding MS
(www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html). Safety was confirmed, and
intensive repeated tests on the patients measuring nerve conduction in various pathways in
the brain and in the spinal cord showed statistically significant improvements at 12 months
in every patient. While highly preliminary and involving only a very small number of
patients, these results at least raise the possibility of a significant (though very partial)
underlying repair effect within the damaged nervous system.
The investigators believe this urgently requires further testing - both to accelerate benefit
for patients, and to begin improving therapeutic efficacy. The investigators therefore
propose a programme of translational and clinical stem cell research, aiming (1) to continue
translation with a phase two controlled trial of bone marrow cells in patients with
longstanding MS; and (2) to explore in parallel the potential mechanisms of action, by
studying bone marrow cells from treated patients and control subjects, aiming to establish
which of the various relevant bone marrow subpopulations contribute to efficacy, and which
particular reparative mechanism(s) are important. The investigators hope these studies will
not only confirm the therapeutic benefit of this approach, but also provide the basis for
improving the magnitude and impact of this novel and exciting treatment modality.
Status | Recruiting |
Enrollment | 80 |
Est. completion date | October 2019 |
Est. primary completion date | October 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - Diagnosis of clinically-definite MS as defined by the McDonald criteria - Aged 18 - 65 years. - EDSS of 4.0 to 6 inclusive - Disease duration >5 years - Disease progression (increase in physical disability, not due to major relapse) in preceding year - Signed, written informed consent - Willing and able to comply with study visits according to protocol for the full study period Exclusion Criteria: - Pregnancy, breastfeeding or lactation - History of autologous/allogenic bone marrow transplantation or peripheral blood stem cell transplant - Bone marrow insufficiency - History of lymphoproliferative disease or previous total lymphoid irradiation - Immune deficiency - Current or recent (<5 years) malignancy - Chronic or frequent drug-resistant bacterial infections or presence of active infection requiring antimicrobial treatment - Frequent and/or serious viral infection - Systemic or invasive fungal disease within 2 years of entry to study - Significant renal, hepatic, cardiac or respiratory dysfunction - Contraindication to anaesthesia - Bleeding or clotting diathesis - Current or recent (within preceding 12 months) immunomodulatory therapy other than corticosteroid therapy - Treatment with corticosteroids within the preceding three months - Significant relapse within preceding 6 months - Predominantly relapsing-remitting disease over preceding 12 months - Radiation exposure in the past year other than chest / dental x-rays - Previous claustrophobia - The presence of any implanted metal or other contraindication to MRI - Participation in another experimental study or treatment within the preceding 24 months |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Southmead Hospital | Bristol |
Lead Sponsor | Collaborator |
---|---|
North Bristol NHS Trust | Bristol Royal Hospital for Children, Catholic Bishops of England and Wales, Friends of Frenchay, Kenneth and Claudia Silverman Family Foundation, Medical Research Council, Multiple Sclerosis Trust, NHS Blood and Transplant, Rosetrees Trust, University of Bristol, University of Nottingham |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Global evoked potential (GEP): mean change from time of marrow infusion to end of study | Multimodal evoked potentials will be examined at 0, 6, 12, 18 and 24 months. Evoked potential abnormalities will be quantified according to a 4-point graded ordinal score modified from Leocani et al (JNNP 2006, 77:1030-1035) (0=normal; 1=increased latency; 2=increased latency and abnormal amplitude; 3=absent). The recording of the evoked potentials shall be in accordance with the Guidelines of the International Federation of Clinical Neurophysiology and analysis will be performed using standard methods. Electrophysiological responses shall be considered abnormal if they exceed 2.5 standard deviations of the normal values or cannot be detected. |
Entry and every 6 months for 2 years | |
Secondary | Safety | Evaluation of number and nature of adverse events | Continuous throughout study period (2 years) | |
Secondary | Expanded disability status scale | Time to EDSS progression of at least one point from a baseline EDSS of 4.0, 4.5 or 5.0 or at least 0.5 points from a baseline EDSS =5.5 | At entry then 6 weeks, 6 months and 1 year after each infusion | |
Secondary | Multiple sclerosis impact scale (MSIS-29) | Mean change from baseline to end of study on the patient-based MSIS-29 scale | At entry then 6 weeks, 6 months and 1 year after each infusion | |
Secondary | Multiple sclerosis functional composite (MSFC) | Mean change on MSFC score from baseline to final visit | At entry then 6 weeks, 6 months and 1 year after each infusion | |
Secondary | MRI head and cord | The secondary MRI outcome measures will relate to 1) lesion load, 2) atrophy measures both of the brain and of cross-sectional area of the spinal cord, and changes in mean diffusivity. Exploratory analysis of the resting-state fMRI data will investigate correlations between network patterns and 'strength' of networks connectivity from the resting-state fMRI with classifications revealed by the various evoked potential studies |
At entry, 1 year and 2 years post-harvest | |
Secondary | Optical coherence tomography | Measurement of retinal nerve fibre layer thickness and macular volume | Entry, 1 year and 2 years post-harvest |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02282826 -
A First-in-human, Single Ascending Dose Study of GZ402668 in Patients With Progressive Multiple Sclerosis
|
Phase 1 | |
Completed |
NCT02804594 -
A Study of Oxidative Pathways in MS Fatigue
|
Phase 2 | |
Completed |
NCT04120675 -
Efficacy of Early Harvest Olive Oil in Cognition of Primary (PPMS) or Secondary (SPMS) Progressive Multiple Sclerosis
|
N/A | |
Completed |
NCT01719159 -
Intrathecal Therapy With Monoclonal Antibodies in Progressive Multiple Sclerosis
|
Phase 2 | |
Enrolling by invitation |
NCT03552211 -
Evaluation of the Incidence of Relapses in Patients With Biotin-treated Progressive Multiple Sclerosis
|
||
Recruiting |
NCT05740722 -
Nicotinamide Riboside Supplementation In Progressive Multiple Sclerosis
|
Phase 2 | |
Completed |
NCT03980145 -
G-EO Gait Rehabilitation Training in Progressive Multiple Sclerosis
|
N/A | |
Completed |
NCT03269071 -
Neural Stem Cell Transplantation in Multiple Sclerosis Patients
|
Phase 1 | |
Not yet recruiting |
NCT05811013 -
Effects of Transcranial Static Magnetic Field Stimulation (tSMS) in Progressive Multiple Sclerosis
|
N/A | |
Not yet recruiting |
NCT04289909 -
Identification of Retinal Perivascular Inflammation in Patients With Multiple Sclerosis Using Adaptive Optics (RETIMUS)
|
N/A | |
Recruiting |
NCT05685784 -
Multiple Sclerosis Prediction and Monitoring of Progression Study
|
N/A | |
Completed |
NCT03493841 -
Comparing Tolerability and Absorption of Racemic and R-lipoic Acid in Progressive Multiple Sclerosis
|
Phase 1 | |
Completed |
NCT03302806 -
Study to Assess Effect and Safety of High Dose of Biotin (Qizenday®) in Progressive Multiple Sclerosis
|
||
Recruiting |
NCT05441488 -
Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis
|
Phase 3 | |
Recruiting |
NCT04695080 -
ChariotMS - Cladribine to Halt Deterioration in People With Advanced Multiple Sclerosis
|
Phase 2/Phase 3 | |
Recruiting |
NCT06451159 -
A Study of KYV-101, a CD19 CAR T Cell Therapy, in Participants With Treatment Refractory Progressive Multiple Sclerosis
|
Phase 1 | |
Completed |
NCT03423121 -
A Trial of Bile Acid Supplementation in Patients With Multiple Sclerosis
|
Phase 1/Phase 2 | |
Terminated |
NCT02580669 -
Study by Magnetic Resonance Imaging in the Progressive Forms of Multiple Sclerosis
|
N/A | |
Enrolling by invitation |
NCT05706220 -
Visual Processing Speed and Objective Analysis of Ocular Movements in Multiple Sclerosis
|
||
Recruiting |
NCT01364246 -
Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Progressive Multiple Sclerosis and Neuromyelitis Optica
|
Phase 1/Phase 2 |