Effect of Fingolimod on Neurodegeneration
Condition: Cognition; Brain Volume Loss
MeSH terms: Nerve Degeneration
Intervention: 0,5 mg Fingolimod
Intervention description: 0.5 mg p.o fingolimod daily
Intervention MeSH terms: Fingolimod Hydrochloride
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: RRMS,; Cognition,; brain,; Fingolimod,; Multiple Sclerosis,; neurodegeneration,; Brain atrophy,; gray matter atrophy,; thalamic atrophy,; biomarkers,; BICAMS Battery,

Summary:

      This was a 24-month, open-label, multicenter study with a single treatment arm design.

      Primary objective of this study was:

      -To investigate the effects of Fingolimod on cognitive performance in highly active relapsing
      remitting multiple sclerosis patients

      Secondary objectives of this study were:

        -  To investigate the correlation between the effect of fingolimod on cognitive
           performances and MRI data.

        -  To evaluate the effect of fingolimod on biomarkers (24 hydroxy cholesterol, osteopontin
           and matrix metalloproteinases) related to neurodegeneration

        -  To investigate the effect of fingolimod on brain gray matter atrophy and thalamic
           atrophy.

      Polulation The hope was to recruit a minimum of 80 relapsing remitting MS (RRMS) patients
      according to the McDonald criteria.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosed with RRMS as described in 2010 McDonald criteria (36)

          2. Provided written informed consent prior to any intervention

          3. Unresponsive to treatment with a beta interferon or glatiramer acetate for a minimum
             of one year at and at adequate dose and with high disease activity .

             (Unresponsive patients: patients with no changes in relapses, increased relapses,
             severer relapses with one-year treatment or those who had had at least one relapse
             during the past one year under previous treatments and one or multiple contrast
             enhancing lesions in cranial MRI or increased T2 lesions in successive MRIs)

          4. EDSS score below 5.5 at screening

        Exclusion Criteria:

          -  1. Patients with primary or secondary progressive or progressive relapsing MS. 2.
             Patients with known contraindications for fingolimod treatment. 3. Other coexistent
             autoimmune diseases including Hashimoto thyroiditis, systemic lupus erythematosus,
             rheumatoid anthiritis, psoriasis etc.

             4. Patients with any of the following cardiovascular conditions:

               -  Resting heart rate < 45 bpm/min

               -  Cardiac failure at any time during the first study visit (Class III as per NYHA
                  classification) or significant heart disease as judged by the physician

               -  Myocardial infarction during the last 6 months

               -  History of Mobitz Type II grade 2 AV block

               -  Past or current grade 3 AV block

               -  Confirmed history of sick sinus syndrome or sino-atrial heart block

               -  arrhythmia requiring current treatment with Class Ia drugs (ajmaline,
                  disopyramid, procainamide, quinidine)

               -  hypertension uncontrolled with medication 5. History of malignancy of any organ
                  system (other than localized basal cell carcinoma of the skin), treated or
                  untreated, within the past 5 years, regardless of whether there is evidence of
                  local recurrence or metastases.

                  6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state
                  of a female after conception and until the termination of gestation, detected by
                  urinalysis and confirmed by a positive hCG laboratory test.

                  7. Negative for varicella-zoster virus IgG antibodies at screening. Patients who
                  have negative results for varicella-zoster virus IgG antibodies can be included
                  in the study after vaccination for varicella-zoster virus.

                  8. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS,
                  Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis
                  B surface antigen or Hepatitis C antibody tests, respectively 9. History of
                  previous fingolimod therapy 10. Patient who received any of the treatments below:

                    1. Corticosteroids or adrenocorticotropic hormone (ACTH) during the last 1
                       month

                    2. Immunosuppressive medications such as azathioprine or methotrexate etc.

                    3. Immunoglobulin treatment during the last 3 months

                    4. Cladribine, cyclophosphamide, mitoxantrone, natalizumab at any time