Clinical trial NCT02575365: Effect of Fingolimod on Neurodegeneration
Official title: Effect of Fingolimod on Neurodegeneration, Brain Atrophy and Cognitive Impairment in Relapsing Remitting Multiple Sclerosis Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cognition
Brain Volume Loss
Keywords: RRMS,
Cognition,
brain,
Fingolimod,
Multiple Sclerosis,
neurodegeneration,
Brain atrophy,
gray matter atrophy,
thalamic atrophy,
biomarkers,
BICAMS Battery,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-10-14
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Change From Baseline in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Battery Test at 12 Months
timeFrame: baseline , month 12.
measure: Change From Baseline in The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Battery Test at 24 Months
timeFrame: baseline and month 24
Secondary outcomes:
measure: Change From Baseline in PASAT Test
timeFrame: baseline ,months 6, month 12 and month 24
measure: Change From Baseline in Stroop Test
timeFrame: baseline, month 6, month 12 and month 24
measure: Change From Baseline in Brain Gray Matter Atrophy and Thalamic Atrophy
timeFrame: baseline, month 6, month 12, month 18 and month 24
measure: Change From Baseline in Serum Levels of 24S-hydroxycholesterol (24OHC) , Osteopontin and Matrix Metalloproteinases (and Also MMPI's)
timeFrame: baseline, month 6, month , month 12 and month 24
measure: the Correlation Between Effect of Fingolimod on Cognitive Performances and Brain Atrophy (Gray Matter Atrophy and Thalamic Atrophy) by Comparing Baseline and Month 24.
timeFrame: baseline, month 24
Other outcomes:
Locations:
city: Bursa
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Kutahya
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: