drugset / Trial / NCT03448159
Fluoxetine Opens Window to Improve Motor Recovery After Stroke
Phase 2
Completed
52 enrolled
University Health Network, Toronto
Applied Health Research Centre · collabBrain Canada · collabDalhousie University · collabHeart and Stroke Foundation of Canada · collabMemorial University of Newfoundland · collabParkwood Hospital, London, Ontario · collabRiverview Health Centre Foundation · collabSunnybrook Health Sciences Centre · collabUniversity of British Columbia · collabUniversity of Calgary · collab
RandomizedParallel-groupQuadruple-blindTreatment
Summary
The FLOW trial is a randomized placebo-controlled trial analyzing the effect of coupling an anti-depressant, fluoxetine (Prozac), and exercise to improve motor recovery following a stroke.
Timeline
- Start
- 2019-01-01
- Primary completion
- 2022-09-30
- Completion
- 2022-09-30
Publications
- Background Alexander LD, Black SE, Patterson KK, Gao F, Danells CJ, McIlroy WE. Association between gait asymmetry and brain lesion location in stroke patients. Stroke. 2009 Feb;40(2):537-44. doi: 10.1161/STROKEAHA.108.527374. Epub 2008 Dec 24.
- Background AVERT Trial Collaboration group. Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial. Lancet. 2015 Jul 4;386(9988):46-55. doi: 10.1016/S0140-6736(15)60690-0. Epub 2015 Apr 16.
- Background Salbach NM, Wood-Dauphinee S, Desrosiers J, Eng JJ, Graham ID, Jaglal SB, Korner-Bitensky N, MacKay-Lyons M, Mayo NE, Richards CL, Teasell RW, Zwarenstein M, Bayley MT; Stroke Canada Optimization of Rehabilitation By Evidence - Implementation Trial (SCORE-IT) Team. Facilitated interprofessional implementation of a physical rehabilitation guideline for stroke in inpatient settings: process evaluation of a cluster randomized trial. Implement Sci. 2017 Aug 1;12(1):100. doi: 10.1186/s13012-017-0631-7.
- Background Bensimon K, Herrmann N, Swardfager W, Yi H, Black SE, Gao FQ, Snaiderman A, Lanctot KL. Kynurenine and depressive symptoms in a poststroke population. Neuropsychiatr Dis Treat. 2014 Sep 22;10:1827-35. doi: 10.2147/NDT.S65740. eCollection 2014.
- Background Berends HI, Nijlant J, van Putten M, Movig KL, IJzerman MJ. Single dose of fluoxetine increases muscle activation in chronic stroke patients. Clin Neuropharmacol. 2009 Jan-Feb;32(1):1-5.
- Background Biernaskie J, Chernenko G, Corbett D. Efficacy of rehabilitative experience declines with time after focal ischemic brain injury. J Neurosci. 2004 Feb 4;24(5):1245-54. doi: 10.1523/JNEUROSCI.3834-03.2004.
- Background Billinger SA, Arena R, Bernhardt J, Eng JJ, Franklin BA, Johnson CM, MacKay-Lyons M, Macko RF, Mead GE, Roth EJ, Shaughnessy M, Tang A; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; Council on Epidemiology and Prevention; Council on Clinical Cardiology. Physical activity and exercise recommendations for stroke survivors: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Aug;45(8):2532-53. doi: 10.1161/STR.0000000000000022. Epub 2014 May 20.
- Background Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002 Apr 11;416(6881):636-40. doi: 10.1038/416636a.
- Background Breceda EY, Dromerick AW. Motor rehabilitation in stroke and traumatic brain injury: stimulating and intense. Curr Opin Neurol. 2013 Dec;26(6):595-601. doi: 10.1097/WCO.0000000000000024.
- Background Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, Loubinoux I. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):123-30. doi: 10.1016/S1474-4422(10)70314-8. Epub 2011 Jan 7.
- Background Cumberland Consensus Working Group; Cheeran B, Cohen L, Dobkin B, Ford G, Greenwood R, Howard D, Husain M, Macleod M, Nudo R, Rothwell J, Rudd A, Teo J, Ward N, Wolf S. The future of restorative neurosciences in stroke: driving the translational research pipeline from basic science to rehabilitation of people after stroke. Neurorehabil Neural Repair. 2009 Feb;23(2):97-107. doi: 10.1177/1545968308326636.
- Background Dhami KS, Churchward MA, Baker GB, Todd KG. Fluoxetine and citalopram decrease microglial release of glutamate and D-serine to promote cortical neuronal viability following ischemic insult. Mol Cell Neurosci. 2013 Sep;56:365-74. doi: 10.1016/j.mcn.2013.07.006. Epub 2013 Jul 19.
- Background Dromerick AW, Edwardson MA, Edwards DF, Giannetti ML, Barth J, Brady KP, Chan E, Tan MT, Tamboli I, Chia R, Orquiza M, Padilla RM, Cheema AK, Mapstone ME, Fiandaca MS, Federoff HJ, Newport EL. Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial. Front Hum Neurosci. 2015 Apr 29;9:231. doi: 10.3389/fnhum.2015.00231. eCollection 2015.
- Background Espinera AR, Ogle ME, Gu X, Wei L. Citalopram enhances neurovascular regeneration and sensorimotor functional recovery after ischemic stroke in mice. Neuroscience. 2013 Sep 5;247:1-11. doi: 10.1016/j.neuroscience.2013.04.011. Epub 2013 Apr 13.
- Background Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
- Background Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, Powers WJ, DeCarli C, Merino JG, Kalaria RN, Vinters HV, Holtzman DM, Rosenberg GA, Wallin A, Dichgans M, Marler JR, Leblanc GG. National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke. 2006 Sep;37(9):2220-41. doi: 10.1161/01.STR.0000237236.88823.47. Epub 2006 Aug 17.
- Background Hackett ML, Duncan JR, Anderson CS, Broad JB, Bonita R. Health-related quality of life among long-term survivors of stroke : results from the Auckland Stroke Study, 1991-1992. Stroke. 2000 Feb;31(2):440-7. doi: 10.1161/01.str.31.2.440.
- Background Harris JE, Eng JJ, Miller WC, Dawson AS. A self-administered Graded Repetitive Arm Supplementary Program (GRASP) improves arm function during inpatient stroke rehabilitation: a multi-site randomized controlled trial. Stroke. 2009 Jun;40(6):2123-8. doi: 10.1161/STROKEAHA.108.544585. Epub 2009 Apr 9.
- Background Hsieh YW, Wang CH, Sheu CF, Hsueh IP, Hsieh CL. Estimating the minimal clinically important difference of the Stroke Rehabilitation Assessment of Movement measure. Neurorehabil Neural Repair. 2008 Nov-Dec;22(6):723-7. doi: 10.1177/1545968308316385. Epub 2008 Sep 5.
- Background Hsueh IP, Hsu MJ, Sheu CF, Lee S, Hsieh CL, Lin JH. Psychometric comparisons of 2 versions of the Fugl-Meyer Motor Scale and 2 versions of the Stroke Rehabilitation Assessment of Movement. Neurorehabil Neural Repair. 2008 Nov-Dec;22(6):737-44. doi: 10.1177/1545968308315999. Epub 2008 Jul 21.
- Background Iadecola C, Anrather J. Stroke research at a crossroad: asking the brain for directions. Nat Neurosci. 2011 Oct 26;14(11):1363-8. doi: 10.1038/nn.2953.
- Background Jorgensen HS, Nakayama H, Raaschou HO, Vive-Larsen J, Stoier M, Olsen TS. Outcome and time course of recovery in stroke. Part I: Outcome. The Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995 May;76(5):399-405. doi: 10.1016/s0003-9993(95)80567-2.
- Background Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H. Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci U S A. 2010 May 4;107(18):8434-9. doi: 10.1073/pnas.0912690107. Epub 2010 Apr 19.
- Background Krakauer JW, Carmichael ST, Corbett D, Wittenberg GF. Getting neurorehabilitation right: what can be learned from animal models? Neurorehabil Neural Repair. 2012 Oct;26(8):923-31. doi: 10.1177/1545968312440745. Epub 2012 Mar 30.
- Background Kwah LK, Harvey LA, Diong J, Herbert RD. Models containing age and NIHSS predict recovery of ambulation and upper limb function six months after stroke: an observational study. J Physiother. 2013 Sep;59(3):189-97. doi: 10.1016/S1836-9553(13)70183-8.
- Background Langdon KD, Corbett D. Improved working memory following novel combinations of physical and cognitive activity. Neurorehabil Neural Repair. 2012 Jun;26(5):523-32. doi: 10.1177/1545968311425919. Epub 2011 Dec 9.
- Background Levine B, Schweizer TA, O'Connor C, Turner G, Gillingham S, Stuss DT, Manly T, Robertson IH. Rehabilitation of executive functioning in patients with frontal lobe brain damage with goal management training. Front Hum Neurosci. 2011 Feb 17;5:9. doi: 10.3389/fnhum.2011.00009. eCollection 2011.
- Background Lynch E, Hillier S, Cadilhac D. When should physical rehabilitation commence after stroke: a systematic review. Int J Stroke. 2014 Jun;9(4):468-78. doi: 10.1111/ijs.12262. Epub 2014 Mar 18.
- Background Mackay-Lyons M, McDonald A, Matheson J, Eskes G, Klus MA. Dual effects of body-weight supported treadmill training on cardiovascular fitness and walking ability early after stroke: a randomized controlled trial. Neurorehabil Neural Repair. 2013 Sep;27(7):644-53. doi: 10.1177/1545968313484809. Epub 2013 Apr 18.
- Background Mansfield A, Wong JS, Bryce J, Brunton K, Inness EL, Knorr S, Jones S, Taati B, McIlroy WE. Use of Accelerometer-Based Feedback of Walking Activity for Appraising Progress With Walking-Related Goals in Inpatient Stroke Rehabilitation: A Randomized Controlled Trial. Neurorehabil Neural Repair. 2015 Oct;29(9):847-57. doi: 10.1177/1545968314567968. Epub 2015 Jan 20.
- Background Maya Vetencourt JF, Sale A, Viegi A, Baroncelli L, De Pasquale R, O'Leary OF, Castren E, Maffei L. The antidepressant fluoxetine restores plasticity in the adult visual cortex. Science. 2008 Apr 18;320(5874):385-8. doi: 10.1126/science.1150516.
- Background McEwen D, Taillon-Hobson A, Bilodeau M, Sveistrup H, Finestone H. Virtual reality exercise improves mobility after stroke: an inpatient randomized controlled trial. Stroke. 2014 Jun;45(6):1853-5. doi: 10.1161/STROKEAHA.114.005362. Epub 2014 Apr 24.
- Background McIntyre A, Richardson M, Janzen S, Hussein N, Teasell R. The evolution of stroke rehabilitation randomized controlled trials. Int J Stroke. 2014 Aug;9(6):789-92. doi: 10.1111/ijs.12272. Epub 2014 Mar 13.
- Background Murphy TH, Corbett D. Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci. 2009 Dec;10(12):861-72. doi: 10.1038/nrn2735. Epub 2009 Nov 4.
- Background Nadeau SE, Wu SS, Dobkin BH, Azen SP, Rose DK, Tilson JK, Cen SY, Duncan PW; LEAPS Investigative Team. Effects of task-specific and impairment-based training compared with usual care on functional walking ability after inpatient stroke rehabilitation: LEAPS Trial. Neurorehabil Neural Repair. 2013 May;27(4):370-80. doi: 10.1177/1545968313481284. Epub 2013 Mar 15.
- Background Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science. 2002 Nov 8;298(5596):1248-51. doi: 10.1126/science.1072699.
- Background Ploughman M, Granter-Button S, Chernenko G, Tucker BA, Mearow KM, Corbett D. Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia. Neuroscience. 2005;136(4):991-1001. doi: 10.1016/j.neuroscience.2005.08.037. Epub 2005 Oct 3.
- Background Ploughman M, Windle V, MacLellan CL, White N, Dore JJ, Corbett D. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke. 2009 Apr;40(4):1490-5. doi: 10.1161/STROKEAHA.108.531806. Epub 2009 Jan 22.
- Background Pollock A, St George B, Fenton M, Firkins L. Top 10 research priorities relating to life after stroke--consensus from stroke survivors, caregivers, and health professionals. Int J Stroke. 2014 Apr;9(3):313-20. doi: 10.1111/j.1747-4949.2012.00942.x. Epub 2012 Dec 11.
- Background Portelli R, Lowe D, Irwin P, Pearson M, Rudd AG; Intercollegiate Stroke Working Party. Institutionalization after stroke. Clin Rehabil. 2005 Jan;19(1):97-108. doi: 10.1191/0269215505cr822oa.
- Background Savitz SI, Cramer SC, Wechsler L; STEPS 3 Consortium. Stem cells as an emerging paradigm in stroke 3: enhancing the development of clinical trials. Stroke. 2014 Feb;45(2):634-9. doi: 10.1161/STROKEAHA.113.003379. Epub 2013 Dec 24. No abstract available.
- Background Scali M, Begenisic T, Mainardi M, Milanese M, Bonifacino T, Bonanno G, Sale A, Maffei L. Fluoxetine treatment promotes functional recovery in a rat model of cervical spinal cord injury. Sci Rep. 2013;3:2217. doi: 10.1038/srep02217.
- Background Soleman S, Yip PK, Duricki DA, Moon LD. Delayed treatment with chondroitinase ABC promotes sensorimotor recovery and plasticity after stroke in aged rats. Brain. 2012 Apr;135(Pt 4):1210-23. doi: 10.1093/brain/aws027. Epub 2012 Mar 6.
- Background Stinear CM, Byblow WD. Predicting and accelerating motor recovery after stroke. Curr Opin Neurol. 2014 Dec;27(6):624-30. doi: 10.1097/WCO.0000000000000153.
- Background Van Breukelen GJ. ANCOVA versus change from baseline: more power in randomized studies, more bias in nonrandomized studies [corrected]. J Clin Epidemiol. 2006 Sep;59(9):920-5. doi: 10.1016/j.jclinepi.2006.02.007. Epub 2006 Jun 23.
- Background Vickers AJ. Analysis of variance is easily misapplied in the analysis of randomized trials: a critique and discussion of alternative statistical approaches. Psychosom Med. 2005 Jul-Aug;67(4):652-5. doi: 10.1097/01.psy.0000172624.52957.a8.
- Background Wade DT, Skilbeck CE, Wood VA, Langton Hewer R. Long-term survival after stroke. Age Ageing. 1984 Mar;13(2):76-82. doi: 10.1093/ageing/13.2.76.
- Background Wahl AS, Omlor W, Rubio JC, Chen JL, Zheng H, Schroter A, Gullo M, Weinmann O, Kobayashi K, Helmchen F, Ommer B, Schwab ME. Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. Science. 2014 Jun 13;344(6189):1250-5. doi: 10.1126/science.1253050.
- Background Wang CH, Hsieh CL, Dai MH, Chen CH, Lai YF. Inter-rater reliability and validity of the stroke rehabilitation assessment of movement (stream) instrument. J Rehabil Med. 2002 Jan;34(1):20-4. doi: 10.1080/165019702317242668.
- Background Wang D, Fawcett J. The perineuronal net and the control of CNS plasticity. Cell Tissue Res. 2012 Jul;349(1):147-60. doi: 10.1007/s00441-012-1375-y. Epub 2012 Mar 23.
- Background Zittel S, Weiller C, Liepert J. Citalopram improves dexterity in chronic stroke patients. Neurorehabil Neural Repair. 2008 May-Jun;22(3):311-4. doi: 10.1177/1545968307312173. Epub 2008 Jan 24.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Fluoxetine | Small molecule | 20 mg | — |