Open Access Highly Accessed Study protocol

Fluoxetine in Progressive Multiple Sclerosis (FLUOX-PMS): study protocol for a randomized controlled trial

Melissa Cambron1*, Jop Mostert2, Patrick Haentjens3, Marie D’Hooghe4, Guy Nagels4, Barbara Willekens5, Dorothea Heersema6, Jan Debruyne7, Wim Van Hecke8, Luc Algoed9, Nina De Klippel10, Erwin Fosselle11, Guy Laureys112, Henri Merckx13, Bart Van Wijmeersch14, Ludo Vanopdenbosch15, Wim Verhagen16, Raymond Hupperts17, Gerald Hengstman18, Veronique Michiels1, Annick Van Merhaegen-Wieleman1 and Jacques De Keyser16

Author Affiliations

1 Department of Neurology, University Hospital Brussel, Center for Neurosciences Vrije Universiteit Brussel (VUB) UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium

2 Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands

3 Centre for Outcomes Research and Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, B 1090 Brussels, Belgium

4 Department of Neurology, National MS Center Melsbroek, Brussels, Belgium

5 Department of Neurology, Antwerp University Hospital, Antwerp, Belgium

6 Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

7 Department of Neurology, University Hospital Ghent, Ghent, Belgium

8 Icometrix, Leuven, Belgium

9 Department of Neurology, AZ Maria Middelares, Ghent, Belgium

10 Department of Neurology, Jessa Hospital, Hasselt, Belgium

11 Department of Neurology, ASZ Aalst, Aalst, Belgium

12 Department of Neurology, Maria Hospital, Halle, Belgium

13 Department of Neurology, H.-Hartziekenhuis, Menen, Belgium

14 Department of Neurology, MS centre, Overpelt, Belgium

15 Department of Neurology, AZ St. Jan, Brugge, Belgium

16 Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

17 Department of Neurology, Orbis Medisch Centrum, Sittard, The Netherlands

18 Department of Neurology, Catharina Ziekenhuis, Eindhoven, The Netherlands

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Trials 2014, 15:37  doi:10.1186/1745-6215-15-37

Published: 25 January 2014

Abstract

Background

Currently available disease-modifying treatments acting by modifying the immune response are ineffective in progressive multiple sclerosis (MS), which is caused by a widespread axonal degeneration. Mechanisms suspected to be involved in this widespread axonal degeneration are reduced axonal energy metabolism, axonal glutamate toxicity, and reduced cerebral blood flow. Fluoxetine might theoretically reduce axonal degeneration in MS because it stimulates energy metabolism through enhancing glycogenolysis, stimulates the production of brain-derived neurotrophic factor, and dilates cerebral arterioles. The current document presents the protocol of a clinical trial to test the hypothesis that fluoxetine slows down the progressive phase of MS.

Methods/Design

The FLUOX-PMS trial is a multi-center, randomized, controlled and double-blind clinical study. A total of 120 patients with the diagnosis of either secondary or primary progressive MS will be treated either by fluoxetine (40 mg daily) or placebo for a total period of 108 weeks. The primary endpoint is the time to confirmed disease progression defined as either at least a 20% increase in the timed 25-Foot Walk or at least a 20% increase in the 9-Hole Peg Test. Secondary endpoints include the Hauser ambulation index, cognitive changes, fatigue, magnetic resonance imaging of the brain, and in a small subgroup optical coherence tomography.

Discussion

The FLUOX-PMS trial will gives us information as to whether fluoxetine has neuroprotective effects in patients with progressive MS.

Trial Registration

Eudra-CT: 2011-003775-11

Keywords:
Multiple sclerosis; Primary progressive; Secondary progressive; Clinical trial; Fluoxetine; Neuroprotection