Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis (BiobankII)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Heinrich-Heine University, Duesseldorf
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT01755871
First received: December 19, 2012
Last updated: November 11, 2014
Last verified: February 2014
  Purpose

The purpose of this study is to explore immunomodulatory and immunosuppressive mechanisms of action of fingolimod in patients with Relapsing remitting multiple Sclerosis to collect data on biomarkers after initiation of fingolimod treatment.


Condition Intervention Phase
Relapsing Remitting Multiple Sclerosis
Drug: Fingolimod
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • Reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-) by examining the blood [ Time Frame: Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment ] [ Designated as safety issue: No ]
    The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+ CD45RA+) and central memory T cells (CCR7+CD45RA-), and an elevation of effector memory T cells (CCR7- CD45RA-)in the blood, and to study the effect of Fingolimod on Th17 cells by studying their signature cytokines (IL-17, IL-21, IL-22) as well as signature transcription factors (ROR-gamma-t, ROR-alpha, STAT3, Runx1) in peripheral venous blood over 2 years versus baseline.


Secondary Outcome Measures:
  • To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod [ Time Frame: Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment ] [ Designated as safety issue: No ]
    To investigate changes from baseline in B Lymphocytes, monocytes and NK cells in the blood after treatment with fingolimod. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).


Other Outcome Measures:
  • Change of the biomarkers BDNF, NGF, CNTF and LIF in the blood during treatment with fingolimod [ Time Frame: Day 0, Day 28, Day 84, Day 168, Day 336, Day 504, Day 672 after treatment ] [ Designated as safety issue: No ]
    The exploratory endpoints are the change from baseline in the biomarkers BDNF, NGF, CNTF and LIF in the blood. The changes in mRNA expression and serum protein levels will be analysed in peripheral blood as a result of fingolimod treatment.


Estimated Enrollment: 250
Study Start Date: January 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fingolimod
Gilenya 0,5mg per day, oral
Drug: Fingolimod
0,5mg Fingolimod once a day
Other Name: Gilenya

Detailed Description:

After treatment with fingolimod the blood of the patients will be collected at different time points to examine the changes of T cells, B cells and biomarkers.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent from patients capable of giving or withholding full informed consent must be obtained before any assessment is performed in this trial.
  2. Male or female subjects aged 18-65 years.
  3. Subjects with relapsing remitting forms of MS defined by 2010 revised McDonald criteria (see Appendix).
  4. Patients with high disease activity despite treatment with a disease modifying therapy (≥ 1 relapse in the previous year, ≥ 9 hyperintense T2 lesions or ≥1 Gd-enhancing lesion or "non-responding" which could be defined as unchanged or increased relapse rate or ongoing severe relapses compared to previous year) or patients with rapidly evolving severe RRMS (e.g. ≥ 2 relapses with disease progression in one year and ≥ 1 Gd-enhancing lesion or with a significant increase in T2 lesions compared to a recent MRI).
  5. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix).
  6. Sufficient ability to read, write, communicate and understand

Exclusion Criteria:

  1. Patients with a manifestation of MS other than relapsing remitting MS.
  2. Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
  3. History or presence of malignancy (other than localized basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the last 5 years
  4. Diabetic patients with moderate or severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c > 7%.
  5. Diagnosis of macular edema during Baseline Visit (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic baseline visit).
  6. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests.
  7. Negative for varicella-zoster virus IgG antibodies at Baseline.
  8. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 1 month prior to baseline.
  9. Patients who have received total lymphoid irradiation or bone marrow transplantation.
  10. Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to baseline.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01755871

Contacts
Contact: Bernd Kieseier, Prof. +492118118973 bernd.kieseier@uni-duessseldorf.de
Contact: Dorothea Schilken, Dr. +492118119500 dorothea.schilken@med.uni-duesseldorf.de

Locations
Germany
Heinrich Heine Universität Düsseldorf Recruiting
Düsseldorf, Nord-Rhein Westfahlen, Germany, 40225
Contact: Bernd Kieseier, Prof.    +492118118973    bernd.kieseier@uni-duesseldorf.de   
Contact: Dorothea Schilken, Dr.    +492118119500    dorothea.schilken@med.uni-duesseldorf.de   
Principal Investigator: Bernd Kieseier, Prof.         
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Novartis Pharmaceuticals
Investigators
Principal Investigator: Bernd Kieseier, Prof. Heinrich Heine Universität Düsseldorf
  More Information

No publications provided

Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT01755871     History of Changes
Other Study ID Numbers: FINGOHHU
Study First Received: December 19, 2012
Last Updated: November 11, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2015