Progressive Multiple Sclerosis
Conditions
Keywords
Progressive multiple sclerosis, Monoclonal antibodies, Mabthera, Intrathecal treatment
Brief summary
This is a is a small scale open phase two interventional study to assess long-term stabilising effects of on neurological symptoms by regular intrathecal administered monoclonal antibodies in progressive multiple sclerosis.
Detailed description
There is presently no efficient therapy available in progressive MS, especially if there is no clear evidence of active inflammatory lesions or exacerbations as part of the disease. There are, however, evidence that some treatment protocols using cytotoxic drugs may to some extent slow down the progressive course. One specific feature of long-standing MS is that inflammatory cells accumulate in the central nervous system(CNS) compartment in the subarachnoid and perivascular spaces and may therefore be hard to reach via standard drug delivery through systemic administration. Administration of substances via the Intrathecal (IT) route, however, have shown to efficiently distribute in the subarachnoid spaces and may therefore be an attractive route of drug delivery
Interventions
DRUGRituximab
25 mg rituximab is injected intrathecally via an Ommaya reservoir once a week for 3 weeks. Patients are then followed for one year.
Sponsors
Västerbotten County Council, Sweden
Anders Svenningsson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Between the age of 18 and 65 years of age (nonfertile women or fertile women with effective contraceptive methods) * Progressive MS since at least three years * Some kind of documented progression of neurological symptoms during the previous two years. * Expanded Disability Status Scale (EDSS) 4,0 - 7.0 (inclusive) (basically spared arm functions) * Conventional therapy not indicated, contraindicated or failed * Judged as compliant with the protocol
Exclusion criteria
* Eligible for any of the conventional MS therapies * Relapsing remitting multiple sclerosis (RRMS) * Bleeding diathesis or medication contraindicating neurosurgical procedures or lumbar puncture * Cognitive defect making informed consent unreliable * Any medical condition contraindicating minor surgical procedures, as judged by anaesthesiologist * Severe, uncontrolled heart disease * Pregnant or lactating women * Patients having contraindication for or otherwise not compliant with MRI investigations * Documented vulnerability to infections * Simultaneous treatment with other immunosuppressive drugs * Documented allergy or intolerance to Rituximab * Severe psychiatric condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events | One year after completed treatment | Feasibility of IT administered monoclonal antibodies |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stabilisation of the neurological deterioration | At 3,6,9,12 month after completed treatment | Questionaires regarding MS quality of life, symptom inventory and fatigue will be used. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunological markers in blood | At 3,6,9,12 month after treatment | I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset |
| Immunological markers in cerebrospinal fluid (CSF) | At 3, 6, 9 12 month after treatment | I.e. absolute numbers of major lymphocyte subset as well as regulatory cell subset |
Countries
Sweden
Outcome results
None listed