Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Oct 9:9:842.
doi: 10.3389/fneur.2018.00842. eCollection 2018.

Disease Modification in Multiple Sclerosis by Flupirtine-Results of a Randomized Placebo Controlled Phase II Trial

Jan Dörr  1 , Klaus-Dieter Wernecke  2 , Jens Würfel  1   3 , Judith Bellmann-Strobl  1   4 , Volker Siffrin  4 , Muriel B Sättler  5 , Mikael Simons  6   7   8 , Andreas Linsa  9   10 , Hayrettin Tumani  11   12 , Friedemann Paul  1   4   13
Affiliations

Disease Modification in Multiple Sclerosis by Flupirtine-Results of a Randomized Placebo Controlled Phase II Trial

Jan Dörr et al. Front Neurol. .

Abstract

Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less accessible to treatment. Based on suggested additional neuroprotective capacities of the orally available non-opioid and centrally acting analgesic drug flupirtine maleate we hypothesized that treatment with flupirtine maleate might be beneficial in MS patients. The flupirtine as oral treatment in multiple sclerosis (FLORIMS) study was a multi-center, randomized and stratified, placebo-controlled double-blind phase II trial to investigate safety and efficacy in terms of clinical and radiographical activity of flupirtine maleate (300 mg per day) given orally for 12 months, add-on to interferon beta 1b subcutaneously in patients with relapsing remitting MS. Due to a substantial delay in recruitment, enrolment of patients was prematurely terminated after randomization of only 30 of the originally planned 80 patients. Of these, 24 regularly terminated study after 12 months of treatment. Data were analyzed as originally planned. Treatment with flupirtine maleate was overall well tolerated. We observed moderate and asymptomatic elevations of liver enzymes in several cases but no overt hepatotoxicity. Neither the intention to treat nor the per protocol analysis revealed any significant treatment effects of flupirtine maleate with respect to occurrence of MS relapses, disability progression, or development of new lesions on cranial MRI. However, substantial methodological limitations need to be considered when interpreting these results. In conclusion, the results of the FLORIMS study neither add further evidence to nor argue against the hypothesized neuroprotective or disease modifying effects of flupirtine maleate in MS.

Keywords: flupirtine; hepatotoxicity; multiple sclerosis; neuroprotection; randomized controlled trail; safety.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Design of the FLORIMS study. scr, screening; EDSS, expanded disability status scale; IFN, interferon; m, month; MRI, magnetic resonance imaging; MSFC, multiple sclerosis functional composite; rand, randomization.
Figure 2
Figure 2
CONSORT flow diagram. ITT, intent to treat; PP, per protocol; n, number.
See this image and copyright information in PMC

References

    1. Trapp BD, Peterson J, Ransohoff RM, Rudick RA, Mörk S, Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. (1998) 338:278–85. - PubMed
    1. Azevedo CJ, Overton E, Khadka S, Buckley J, Liu S, Sampat M, et al. . Early CNS neurodegeneration in radiologically isolated syndrome. Neurol Neuroimmunol Neuroinflamm. (2015) 2:e102. 10.1212/NXI.0000000000000102 - DOI - PMC - PubMed
    1. Bjartmar C, Kidd G, Mörk S, Rudick R, Trapp BD. Neurological disability correlates with spinal cord axonal loss and reduced N-acetyl aspartate in chronic multiple sclerosis patients. Ann Neurol. (2000) 48:893–901. 10.1002/1531-8249(200012)48:6<893::AID-ANA10>3.0.CO;2-B - DOI - PubMed
    1. De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, et al. . Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. results of a longitudinal magnetic resonance spectroscopy study. Brain (1998) 121(Pt. 8):1469–77. - PubMed
    1. Rottlaender A, Kuerten S. Stepchild or prodigy? Neuroprotection in multiple sclerosis (MS) research. Int J Mol Sci. (2015) 16:14850–65. 10.3390/ijms160714850 - DOI - PMC - PubMed

LinkOut - more resources