Fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH): study protocol for a randomized, double-blind, placebo-controlled, multicenter trial

Juan Manuel Marquez-Romero, Antonio Arauz, José Luis Ruiz-Sandoval, Erick de la Cruz-Estrada, Maria Raquel Huerta-Franco, Gerónimo Aguayo-Leytte, Angélica Ruiz-Franco, Humberto Silos, Juan Manuel Marquez-Romero, Antonio Arauz, José Luis Ruiz-Sandoval, Erick de la Cruz-Estrada, Maria Raquel Huerta-Franco, Gerónimo Aguayo-Leytte, Angélica Ruiz-Franco, Humberto Silos

Abstract

Background: Spontaneous, nontraumatic intracerebral hemorrhage (ICH) is a subtype of stroke that causes a great amount of disability and economic and social burden. This is particularly true in developing countries where it accounts for between 20% and 50% of all strokes. Pharmacological and surgical interventions have been attempted to reduce the mortality and disability caused by ICH, with unsuccessful results. Recently, the use of fluoxetine in addition to physical rehabilitation has been proven useful to improve motor recovery following cerebral infarct. The purpose of this study is to test whether a 3-month treatment with fluoxetine enhances motor recovery in nondepressed patients with acute intracerebral hemorrhage.

Methods/design: Our study is a randomized, double-blind, placebo-controlled, multicenter clinical trial. We will recruit 86 patients with intracerebral hemorrhage of both sexes, aged >18 years, from four Mexican hospitals. The patients will receive either 20 mg of fluoxetine or a placebo once daily for 90 days. The primary outcome is the mean change in the Fugl-Meyer Motor Scale score between inclusion (day 0) and day 90. The secondary outcomes will be changes in the Barthel Index, the Modified Rankin scale and the National Institutes of Health stroke scale. The outcomes will be measured at day 42 ± 7 days and at day 90, for a total of four visits with each subject (at screening and at 0, 42 and 90 days).

Discussion: Current guidelines recommend early supported hospital discharge and home-based rehabilitation programs as the only cost-effective intervention to aid the recovery of patients with intracerebral hemorrhage. Nevertheless, such interventions are dependent on available resources and funding, which make them very difficult to implement in developing countries. We believe that the identification of a helpful pharmacological intervention to aid the motor recovery of these patients will constitute a breakthrough that will have a major impact in reducing the burden of disease caused by this subtype of stroke worldwide, especially in the developing world.

Trial registration: Current Controlled Trials NCT01737541.

Figures

Figure 1
Figure 1
Flowchart of the fluoxetine for motor recovery after acute intracerebral hemorrhage (FMRICH) clinical trial.

References

    1. Morgenstern LB, Hemphill JC 3rd, Anderson C, Becker K, Broderick JP, Connolly ES Jr, Greenberg SM, Huang JN, MacDonald RL, Messe SR, Mitchell PH, Selim M, Tamargo RJ. American Heart Association Stroke Council and Council on Cardiovascular Nursing. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association . Stroke. 2010;41:2108–2129. doi: 10.1161/STR.0b013e3181ec611b.
    1. Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001;344:1450–1460. doi: 10.1056/NEJM200105103441907.
    1. Saposnik G, Del Brutto OH. Stroke in South America: a systematic review of incidence, prevalence, and stroke subtypes. Stroke. 2003;34:2103–2107. doi: 10.1161/01.STR.0000088063.74250.DB.
    1. Zahuranec DB, Brown DL, Lisabeth LD, Gonzales NR, Longwell PJ, Eden SV, Smith MA, Garcia NM, Morgenstern LB. Differences in intracerebral hemorrhage between Mexican Americans and non-Hispanic whites. Neurology. 2006;66:30–34. doi: 10.1212/01.wnl.0000191402.41914.d2.
    1. Romano JG, Arauz A, Koch S, Dong C, Marquez JM, Artigas C, Merlos M, Hernandez B, Roa LF, Rundek T, Sacco RL. Disparities in Stroke Type and Vascular Risk Factors Between 2 Hispanic Populations in Miami and Mexico City. J Stroke Cerebrovasc Dis. 2012. Epub ahead of print.
    1. Steiner T, Petersson J, Al-Shahi Salman R, Christensen H, Cordonnier C, Csiba L, Harnof S, Krieger D, Mendelow D, Molina C, Montaner J, Overgaard K, Roine RO, Schmutzhard E, Tatlisumak T, Toni D, Stapf C. European Research Network on Intracerebral Haemorrhage. European research priorities for intracerebral haemorrhage . Cerebrovasc Dis. 2011;32:409–419. doi: 10.1159/000330653.
    1. Staykov D, Huttner HB, Kohrmann M, Bardutzky J, Schellinger PD. Novel approaches to the treatment of intracerebral haemorrhage. Int J Stroke. 2010;5:457–465. doi: 10.1111/j.1747-4949.2010.00487.x.
    1. Dam M, Tonin P, De Boni A, Pizzolato G, Casson S, Ermani M, Freo U, Piron L, Battistin L. Effects of fluoxetine and maprotiline on functional recovery in poststroke hemiplegic patients undergoing rehabilitation therapy. Stroke. 1996;27:1211–1214. doi: 10.1161/01.STR.27.7.1211.
    1. Pariente J, Loubinoux I, Carel C, Albucher JF, Leger A, Manelfe C, Rascol O, Chollet F. Fluoxetine modulates motor performance and cerebral activation of patients recovering from stroke. Ann Neurol. 2001;50:718–729. doi: 10.1002/ana.1257.
    1. Zittel S, Weiller C, Liepert J. Citalopram improves dexterity in chronic stroke patients. Neurorehabil Neural Repair. 2008;22:311–314. doi: 10.1177/1545968307312173.
    1. Acler M, Robol E, Fiaschi A, Manganotti P. A double blind placebo RCT to investigate the effects of serotonergic modulation on brain excitability and motor recovery in stroke patients. J Neurol. 2009;256:1152–1158. doi: 10.1007/s00415-009-5093-7.
    1. 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;10:123–130. doi: 10.1016/S1474-4422(10)70314-8.
    1. Mikami K, Jorge RE, Adams HP Jr, Davis PH, Leira EC, Jang M, Robinson RG. Effect of antidepressants on the course of disability following stroke. Am J Geriatr Psychiatr. 2011;19:1007–1015. doi: 10.1097/JGP.0b013e31821181b0.
    1. Fugl-Meyer AR, Jaasko L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7:13–31.
    1. Mahoney FI, Barthel DW. Functional Evaluation: The Barthel Index. Md State Med J. 1965;14:61–65.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. López-Roig S, Terol MC, Pastor-Mira MA, Neipp MC, Massutí B, Rodríguez-Marín J. Anxiety and Depression. The HAD scale validation in cancer patients. Revista de Psicología de la Salud. 2000;12:127–155.
    1. Aben I, Verhey F, Lousberg R, Lodder J, Honig A. Validity of the beck depression inventory, hospital anxiety and depression scale, SCL-90, and hamilton depression rating scale as screening instruments for depression in stroke patients. Psychosomatics. 2002;43:386–393. doi: 10.1176/appi.psy.43.5.386.
    1. Kelly PJ, Furie KL, Shafqat S, Rallis N, Chang Y, Stein J. Functional recovery following rehabilitation after hemorrhagic and ischemic stroke. Arch Phys Med Rehabil. 2003;84:968–972. doi: 10.1016/S0003-9993(03)00040-6.
    1. Schepers VP, Ketelaar M, Visser-Meily AJ, de Groot V, Twisk JW, Lindeman E. Functional recovery differs between ischaemic and haemorrhagic stroke patients. J Rehabil Med. 2008;40:487–489. doi: 10.2340/16501977-0198.
    1. Katrak PH, Black D, Peeva V. Do stroke patients with intracerebral hemorrhage have a better functional outcome than patients with cerebral infarction? PM R. 2009;1:427–433. doi: 10.1016/j.pmrj.2009.03.002.
    1. Nannetti L, Paci M, Pasquini J, Lombardi B, Taiti PG. Motor and functional recovery in patients with post-stroke depression. Disabil Rehabil. 2005;27:170–175. doi: 10.1080/09638280400009378.
    1. Rost NS, Smith EE, Chang Y, Snider RW, Chanderraj R, Schwab K, FitzMaurice E, Wendell L, Goldstein JN, Greenberg SM, Rosand J. Prediction of functional outcome in patients with primary intracerebral hemorrhage: the FUNC score. Stroke. 2008;39:2304–2309. doi: 10.1161/STROKEAHA.107.512202.
    1. Jang SH, Kim SH, Cho SH, Choi BY, Cho YW. Demonstration of motor recovery process in a patient with intracerebral hemorrhage. NeuroRehabilitation. 2007;22:141–145.
    1. Ward NS, Newton JM, Swayne OB, Lee L, Thompson AJ, Greenwood RJ, Rothwell JC, Frackowiak RS. Motor system activation after subcortical stroke depends on corticospinal system integrity. Brain. 2006;129:809–819. doi: 10.1093/brain/awl002.
    1. Cho SH, Kim SH, Choi BY, Kang JH, Lee CH, Byun WM, Jang SH. Motor outcome according to diffusion tensor tractography findings in the early stage of intracerebral hemorrhage. Neurosci Lett. 2007;421:142–146. doi: 10.1016/j.neulet.2007.04.052.
    1. Sharma N, Cohen LG. Recovery of motor function after stroke. Dev Psychobiol. 2012;54:254–262. doi: 10.1002/dev.20508.
    1. Gonzenbach RR, Taegtmeyer AB, Luft A, Russmann S. Fluoxetine and motor recovery after ischaemic stroke. Lancet Neurol. 2011;10:499–500. author reply 500-501.
    1. Ruiz-Sandoval JL, Chiquete E, Garate-Carrillo A, Ochoa-Guzman A, Arauz A, Leon-Jimenez C, Carrillo-Loza K, Murillo-Bonilla LM, Villarreal-Careaga J, Barinagarrementeria F, Cantu-Brito C. Spontaneous intracerebral hemorrhage in Mexico: results from a Multicenter Nationwide Hospital-based Registry on Cerebrovascular Disease (RENAMEVASC) Rev Neurol. 2011;53:705–712.
    1. Ferri CP, Schoenborn C, Kalra L, Acosta D, Guerra M, Huang Y, Jacob KS, Llibre Rodriguez JJ, Salas A, Sosa AL, Williams JD, Liu Z, Moriyama T, Valhuerdi A, Prince MJ. Prevalence of stroke and related burden among older people living in Latin America, India and China . J Neurol Neurosurg Psychiatry. 2011;82:1074–1082. doi: 10.1136/jnnp.2010.234153.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться