An observational study in Relapsing-Remitting Multiple Sclerosis, sponsored by Charite University, Berlin, Germany. Terminated at 1 site in Germany. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2021-07-29.
Sponsored by Charite University, Berlin, Germany · Observational
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.
In the past decade, it has become evident that natural killer (NK) cells are more than simply killers and seem to be involved in the regulation of autoimmune conditions such as Multiple Sclerosis (MS). Yet, the complexity of NK cell activation and maturation is only now being understood. Several recent publications have reported on markers characterizing different stages of human NK cell maturation/ differentiation, including CD27, CD62L, CD94 and CD57. In our more recent study, the investigators demonstrated that the chemokine receptor CX3CR1 represents an additional marker for NK cells, which in conjunction with other novel markers, serves to delineate the sequential stages of human NK cell differentiation. CX3CR1 has been suggested to be essential for the protective effects of NK cells in the animal model of MS. In this context, the investigators previously reported on the correlation of the frequency of circulating CX3CR1-positive NK cells with disease activity in patients with MS. Moreover, our unpublished data indicates an association of genetic variation in NK cell-related genes and response to IFN-beta treatment. Thus, it appears that NK cells (or at least certain NK cell fractions) may be not only protective in MS but also mediators of therapeutic benefits.
Fingolimod (GILENYA®) is a modulator of the sphingosine 1-phosphate receptor (S1P-receptors) indicated for the treatment of patients with relapsing forms of MS to reduce the frequency of clinical relapses. Gilenya® is licensed in Germany since April 2011 as an escalation therapy for patients with highly active RRMS.
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. However, this latter study exclusively compared frequencies of NK cells in untreated MS patients and patients treated with fingolimod, while longitudinal intraindividual data during treatment was not presented.
Moreover, these two studies have not considered the potential diverse effects of fingolimod on different NK cells subpopulations. 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.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 21 is below the median of 100 across 1,016 observational studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Charite University, Berlin, Germany is the lead sponsor of 836 studies on the registry; 129 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Definite diagnosis of Relapsing-Remitting Multiple Sclerosis according to the 2010 revised McDonald criteria (Polman et al., 2011)
Exclusion Criteria:
Indication for on-label treatment with fingolimod (Gilenya®) according to the current approval
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.
Time frame: Baseline to (12 months) treatment
NK cell frequency
NK cell frequency at all time points (determined by flow cytometry)
Time frame: Baseline, +1 mo, +3 mo, +6 mo, +12 mo
Percentage immature NK cells/total NK cells
Percentage immature NK cells/total NK cells at all time points
Time frame: Baseline, +1 mo, +3 mo, +6 mo, +12 mo
NK cell activation
NK cell activation (expression of certain cell surface markers determined by flow cytometry) at all time points
Time frame: Baseline, +1 mo, +3 mo, +6 mo, +12 mo
NK cell maturation and activation
NK cell maturation and activation in relation to clinically detectable therapeutic effect (determined a) by annual relapse rate over study period vs. annualized relapse rate in the preceding two years; and b) by the development of disability (determined by Expanded Disability Status Scale (EDSS) during treatment with fingolimod)
Time frame: Baseline, +1 mo, +3 mo, +6 mo, +12 mo
NK cell cytotoxicity and the cytokine production
NK cell cytotoxicity and the cytokine production (IL-15, IL-13, IL-5, GM-CSF, IFN-gamma)
Time frame: Baseline, +1 mo, +3 mo, +6 mo, +12 mo
This study is terminated, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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Charite University, Berlin, Germany