Melissa Cambron1, Jop Mostert2, Marie D'Hooghe3, Guy Nagels3, Barbara Willekens4, Jan Debruyne5, Luc Algoed6, Wim Verhagen7, Raymond Hupperts8, Dorothea Heersema9, Jacques De Keyser10. 1. Department of Neurology, UZ Brussel, Brussel, Belgium/Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB), Brussels, Belgium/ Department of Neurology, AZ Sint-Jan, Bruges, Belgium. 2. Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands. 3. Department of Neurology, UZ Brussel, Brussel, Belgium/Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB), Brussels, Belgium/Nationaal MS Centrum Melsbroek, Steenokkerzeel, Belgium. 4. Department of Neurology, University Hospital Antwerp, Antwerp, Belgium. 5. Department of Neurology, University Hospital Gent, Gent, Belgium. 6. Department of Neurology, AZ Maria Middelares, Gent, Belgium. 7. Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands. 8. Department of Neurology, Zuyderland Medisch Centrum, Sittard-Geleen, The Netherlands. 9. Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 10. Department of Neurology, UZ Brussel, Brussel, Belgium/Center for Neurosciences (C4N) Vrije Universiteit Brussel (VUB), Brussels, Belgium/ Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract
BACKGROUND: Preclinical studies suggest that fluoxetine has neuroprotective properties that might reduce axonal degeneration in multiple sclerosis (MS). OBJECTIVE: To determine whether fluoxetine slows accumulation of disability in progressive MS. METHODS: In a double-blind multicenter phase 2 trial, patients with primary or secondary progressive MS were randomized to fluoxetine 40 mg/day or placebo for a period of 108 weeks. Clinical assessments were performed every 12 weeks by trained study nurses who visited the patients at their home. The primary outcome was the time to a 12-week confirmed 20% increase in the Timed 25 Foot Walk or 9-Hole Peg test. Secondary outcomes included the Hauser ambulation index, cognitive tests, fatigue, and brain magnetic resonance imaging (MRI). RESULTS: In the efficacy analysis, 69 patients receivedfluoxetine and 68 patients received placebo. Using the log-rank test (p = 0.258) and Cox regression analysis (p = 0.253), we found no significant difference in the primary outcome between the two groups. Due to an unexpected slow rate of progression in the placebo group, there was insufficient statistical power to detect a potential benefit of fluoxetine. We found no differences between the two groups for secondary outcomes. CONCLUSION: The trial failed to demonstrate a neuroprotective effect of fluoxetine in patients with progressive MS.
RCT Entities:
BACKGROUND: Preclinical studies suggest that fluoxetine has neuroprotective properties that might reduce axonal degeneration in multiple sclerosis (MS). OBJECTIVE: To determine whether fluoxetine slows accumulation of disability in progressive MS. METHODS: In a double-blind multicenter phase 2 trial, patients with primary or secondary progressive MS were randomized to fluoxetine 40 mg/day or placebo for a period of 108 weeks. Clinical assessments were performed every 12 weeks by trained study nurses who visited the patients at their home. The primary outcome was the time to a 12-week confirmed 20% increase in the Timed 25 Foot Walk or 9-Hole Peg test. Secondary outcomes included the Hauser ambulation index, cognitive tests, fatigue, and brain magnetic resonance imaging (MRI). RESULTS: In the efficacy analysis, 69 patients received fluoxetine and 68 patients received placebo. Using the log-rank test (p = 0.258) and Cox regression analysis (p = 0.253), we found no significant difference in the primary outcome between the two groups. Due to an unexpected slow rate of progression in the placebo group, there was insufficient statistical power to detect a potential benefit of fluoxetine. We found no differences between the two groups for secondary outcomes. CONCLUSION: The trial failed to demonstrate a neuroprotective effect of fluoxetine in patients with progressive MS.
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