Monitoring Natural Killer Cells in Multiple Sclerosis Patients Treated With Fingolimod

NCT01790269 | Terminated

• 1 other identifier: NKcells Gilenya®-treated MS
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Data on fingolimod effects on NK cells are so far conflicting. A longitudinal study on fingolimod treated kidney transplant patients showed that NK cells were not influenced in any of the treatment groups. However, more recent reports indicate an increased frequency of NK cells in peripheral blood and CSF of MS patients treated with fingolimod and a relative reduction of immature CD56bright NK cells in fingolimod-treated MS patients. It has been demonstrated that the expression of NK cell relevant sphingosine 1-phosphate (S1P) receptors seems to increase during NK cell maturation. Thus, different NK cell sub-types may response differently to S1P-receptor agonist such as fingolimod. Therefore, the investigators aim to investigate longitudinally (baseline vs. treatment) the effects of fingolimod on NK cell maturation/differentiation.

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Relapsing-Remitting Multiple Sclerosis; NK cells; Fingolimod

Outcome Measures

Primary Outcomes (1)

• Status of NK cell maturation

  Status of NK cell maturation, defined as the ratio immature NK cells / total NK cells (percentage), before fingolimod treatment vs. after 12 months of treatment (V4). The maturation status is determined by the expression of certain cell surface markers which can be evaluated by flow cytometry.

  Baseline to (12 months) treatment

Secondary Outcomes (5)

• NK cell frequency

  Baseline, +1 mo, +3 mo, +6 mo, +12 mo

• Percentage immature NK cells/total NK cells

  Baseline, +1 mo, +3 mo, +6 mo, +12 mo

• NK cell activation

  Baseline, +1 mo, +3 mo, +6 mo, +12 mo

• NK cell maturation and activation

  Baseline, +1 mo, +3 mo, +6 mo, +12 mo

• NK cell cytotoxicity and the cytokine production

  Baseline, +1 mo, +3 mo, +6 mo, +12 mo

Study Arms (1)

fingolimod treated patients

Indication for on-label treatment with fingolimod (Gilenya®) according to the current approval

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Definite diagnosis of Relapsing-Remitting Multiple Sclerosis according to the 2010 revised McDonald criteria (Polman et al., 2011)

You may qualify if:

• Definite diagnosis of RRMS according to the 2010 revised McDonald criteria (Polman et al., 2011)
• to 64 years old
• Indication for on-label treatment with fingolimod (Gilenya®) ac-cording to the current approval
• EDSS score ≤ 6,0
• Neurological stable with no evidence of relapse or corticosteroid treatment within 30 days prior to screening
• Ability to provide written informed consent
• Highly effective contraception (Pearl Index \< 1), reliable abstinence from any heterosexual relationships, or sterilization of the only partner in women of childbearing potential
• Negative pregnancy test (HCG rapid test in the urine) at screening and baseline in women of childbearing potential

You may not qualify if:

• Patients with MS manifestations other than RRMS
• Patients with known contraindications to Gilenya® according to the current "Fachinformation", in particular
• Immunodeficiency syndrome
• Increased risk of opportunistic infections
• Severe active or chronic active infections (hepatitis, tuberculosis)
• History or presence of malignancy (other than localized basal or squamous cell carcinoma of the skin). Severe liver dysfunction (Child Pugh C)
• Hypersensitivity against active or any other compound of study medication
• nd degree Mobitz Type II or higher degree AV block, Sick-sinus syndrome, or Sinuatrial heart block, Significant QT prolongation (QTc\>470 msec (female) or \>450 msec (males))
• History of symptomatic bradycardia or recurrent syncope, known ischaemic heart disease, cerebrovascular disease, history of myocardial infarction, hypokalaemia, congestive heart failure, history of cardiac arrest, uncontrolled hypertension, or severe sleep apnea. Patients with clinically significant liver, kidney or bone marrow dysfunction, defined by the following laboratory values at the time of screening:
• HB \<8.5 g / dl
• WBC \<2.5 / nl
• platelets \<100/nl
• creatinine clearance by Cockroft-Gault formula: Cl \<110ml/min (men) and Cl \<95ml/min (women), from age of 30 limit drops 10ml/min per decade
• AST / ALT\> 3.5 times higher than the upper reference value
• bilirubin \> 2.0 mg / dl

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Dr. Carmen Infante-Duarte: collaborator

Study Sites (1)

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Jan-Markus Dörr, MD

  Charite Universitätsmedizin Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 13, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: July 29, 2021

Record last verified: 2021-07

Locations

DE (1)