Chronic inflammatory demyelinating polyradiculoneuropathy
Conditions
Interventions
Product Name: Maxtrex Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Methotrexate ph. Eur.
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Pharmaceut
Sponsors
Guy's & St Thomas's NHS Foundation Trust
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women aged >18 years 2. Diagnosis of CIDP by a consultant neurologist with a special interest in peripheral neuropathy 3. Chronically progressive, stepwise, or recurrent weakness, with or without sensory dysfunction, of all extremities, developing over at least 2 months 4. Absent or reduced tendon reflexes 5. Ongoing treatment with at least one of IVIg (equivalent to at least 0.4 g/kg every 4 weeks) or corticosteroid (equivalent to at least prednisolone 15 mg daily). The dose must have been stable (within 25%) for at least 12 weeks and not changed for the past 4 weeks. Patients who are going to withdraw from IVIg in the trial must be receiving it at least every 8 weeks. 6. Duration not less than 6 months 7. At least moderate disability in arms or legs (overall neuropathy disability scale (ONLS) which has been very slightly modified from the INCAT overall disability status scale grade 2) and MRC grade 4 or less weakness in at least one muscle at baseline OR following reduction of steroid or IVIg dose at some time during the past 12 months. 8. Fulfillment of definite or neurophysiological criteria10 proposed by INCAT or EFNS/PNS (Appendix 1) within the past 3 years. In some centres, nerve conduction data as specified in the EFNS/PNS criteria will be collected at the screening or baseline visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnancy, planned pregnancy, breast feeding or unwillingness to practice contraception. 2. Severe concurrent medical conditions which would prevent treatment or assessment, including significant haematological, renal, liver function (including liver enzymes >twice the upper limit of normal) or chest radiograph abnormalities. 3. Alternative cause of peripheral neuropathy such as drug or toxin, hereditary neuropathy or concomitant diseases such as HIV infection, Lyme disease, chronic active hepatitis, systemic lupus erythematosus, IgM paraprotein with anti-MAG antibodies, vasculitis, hematological and non-hematological malignancies. Diabetes mellitus will not be an exclusion criterion. IgG, IgA and IgM paraproteins without anti-MAG antibodies will not be exclusion criteria. 4. Presence of neurogenic sphincter disturbance. 5. Multifocal motor neuropathy (fulfilling proposed EFNS/PNS criteria Appendix 2). 6. Atypical CIDP with pure sensory or persistent unifocal impairment or significant CNS involvement. 7. Immunomodulatory treatment other than IVIg or corticosteroids during the previous 12 weeks. Treatment with methotrexate at any time. 8. Participation in a controlled trial of an investigational medicinal product within the past 12 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does methotrexate decrease the requirement for corticosteroids or intravenous immunoglobulin (IVIg) in patients with (CIDP) who have improved with such treatment and are still receiving it, while improving or at least maintaining levels of impairment and disability?;Secondary Objective: Is change in dose of or is change in impairment or disability the most responsive outcome measure? ;Primary end point(s): Our preferred primary outcome measure would have been change in disability but it is considered likely that participants will be receiving optimal doses of corticosteroids or IVIg and that opportunity for additional improvement will be limited which will make the detection of improvement difficult. The same argument applies to the use of change in impairment. Both of these will be captured as secondary outcome measures after 16 weeks. We have therefore selected change in percentage dose of corticosteroid between the beginning and end of the trial as the primary outcome measure but set procedures for prescription of corticosteroids or IVIg which are designed to prevent deterioration, ie Percentage change in mean weekly dose of corticosteroid or IVIg during weeks 37 – 40 compared with weeks 1 – 4. | — |
Countries
Belgium, Italy, United Kingdom
Outcome results
None listed