Fluoxetine in progressive multiple sclerosis (FLUOX-PMS): study protocol for a randomized controlled trial.
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
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.


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


BACKGROUND
Eudra-CT: 2011-003775-11.
Department of Neurology, University Hospital Brussel, Center for Neurosciences Vrije Universiteit Brussel (VUB) UZ Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. melissa.cambron@gmail.com.
Melissa
M
Cambron
Jop
J
Mostert
Patrick
P
Haentjens
Marie
M
D'Hooghe
Guy
G
Nagels
Barbara
B
Willekens
Dorothea
D
Heersema
Jan
J
Debruyne
Wim
W
Van Hecke
Luc
L
Algoed
Nina
N
De Klippel
Erwin
E
Fosselle
Guy
G
Laureys
Henri
H
Merckx
Bart
B
Van Wijmeersch
Ludo
L
Vanopdenbosch
Wim
W
Verhagen
Raymond
R
Hupperts
Gerald
G
Hengstman
Veronique
V
Michiels
Annick
A
Van Merhaegen-Wieleman
Jacques
J
De Keyser
D000328:Adult; D000368:Aged; D001530:Belgium; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D002985:Clinical Protocols; D003071:Cognition; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D009410:Nerve Degeneration; D009426:Netherlands; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011859:Radiography; D012107:Research Design; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D005473:Fluoxetine