Escitalopram and Language Intervention for Subacute Aphasia

Официальное название

Escitalopram and Language Intervention for Subacute Aphasia (ELISA)

Обзор

In this project, the investigators will investigate the effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on augmenting language therapy effectiveness, as measured by naming untrained pictures and describing pictures, in individuals with aphasia in the acute and subacute post stroke period (i.e., within three months post stroke).

Подробное описание

In this project, the investigators will investigate the effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on augmenting language therapy effectiveness, as measured by naming untrained pictures and describing pictures, in individuals with aphasia in the acute and subacute post stroke period (i.e., within three months post stroke). There has been no previous randomized controlled trial (RCT) to evaluate the effect of daily SSRI in the first three months after stroke on improvement of language in people undergoing aphasia treatment. It is plausible that SSRIs, which elevate synaptic serotonin, might enhance recovery by augmenting synaptic plasticity.

The investigators propose to conduct a Phase 2 multi-center, randomized, double blind, placebo-controlled trial of escitalopram for augmenting language intervention in subacute stroke. The investigators hypothesize that daily escitalopram for 90 days after stroke results in greater improvement (compared to placebo) in naming untrained pictures, as well as greater increase in content of picture description and greater improvement in morphosyntactic production, when combined with speech and language treatment (SALT). A second aim is to evaluate the mechanisms of language recovery in individuals who receive active medical treatment and those who receive placebo, using resting state functional magnetic resonance imaging (rsfMRI) and genetic testing. The investigators hypothesize that greater improvement in language is associated with increased connectivity within the left hemisphere language network on rsfMRI in participants who receive escitalopram than in those who receive placebo, independently of improvement in depression. The investigators also hypothesize that the effects are greatest in individuals with val/val allele of brain-derived neurotrophic factor (BDNF) - (consistent with previous studies showing a greater response to treatment and greater neuroplasticity in people with the val/val allele than those with one or more met alleles.

Вмешательства

• Препарат Escitalopram 10mg
  Escitalopram tablet
• Препарат Placebo
  Sugar pill manufactured to mimic escitalopram 10 mg tablet
• Поведенческое Computer-delivered naming treatment
  15 45-minute sessions of computer-delivered naming treatment beginning two months following stroke

Первичные конечные точки

• Change in Philadelphia Naming Test short-form accuracy score [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]

Вторичные конечные точки (12)

• Language production as assessed by lexical features of discourse in "Cookie Theft" picture description [Срок оценки: Baseline, 5 weeks after computer-delivered naming treatment]
• Language production as assessed by content units included in picture description of "Cookie Theft" [Срок оценки: Baseline, 5 weeks after computer-delivered naming treatment]
• Language production as assessed by rate of syllables per content unit produced in "Cookie Theft" picture description [Срок оценки: Baseline, 5 weeks after computer-delivered naming treatment]
• Depression as assessed by Patient Health Questionnaire (PHQ-9) [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Language production as assessed by Morphosyntactic Generation (MorGen) Test [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Stroke severity as assessed by NIH Stroke Scale (NIHSS) [Срок оценки: Baseline, 5 weeks after computer-delivered naming treatment, 20 weeks after computer-delivered naming treatment]
• Post-stroke level of disability as assessed by modified Rankin Scale (mRS) [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Stroke paresis severity as assessed by right hand strength [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Stroke paresis severity as assessed by right hand dexterity [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Change in new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella" [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Change in incidence of new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella" [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]
• Change in language production as assessed by speech errors produced during the story retelling of "Cinderella" [Срок оценки: Baseline, 1 week after computer-delivered naming treatment]

Критерии участия

Критерии включения

• Participants must have sustained an acute ischemic left hemisphere stroke.
• Participants must be fluent speakers of English by self-report.
• Participants must be capable of giving informed consent or indicating a legally authorized representative to provide informed consent.
• Participants must be age 18 or older.
• Participants must be within 5 days of onset of stroke.
• Participants must be pre-morbidly right-handed by self-report.
• Participants must have an aphasia diagnosis as confirmed by the Western Aphasia Battery-Revised (Aphasia Quotient < 93.8).

Критерии исключения

• Previous neurological disease affecting the brain including previous symptomatic stroke
• Diagnosis of schizophrenia, autism, or other psychiatric or neurological condition that affects naming/language
• A history of additional risk factors for torsades de pointes (TdP; e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Current severe depression, defined as a score of > 15 on the Patient Health Questionnaire (PHQ-9)
• Uncorrected visual loss or hearing loss by self-report
• Use of any medication approved by the FDA for treatment of depression at the time of stroke onset
• Concomitant use of any monoamine oxidase inhibitors (MAOIs) or pimozide, or other drugs that prolong the QT/QTc interval, triptans (and other 5-Hydroxytryptamine Receptor Agonists), or other contraindications to escitalopram that may be identified.
• A QTc greater than 450 milliseconds on electrocardiogram or evidence of hyponatremia (Na < 130) at baseline
• Pregnancy at the time of stroke or planning to become pregnant during the study term.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Johns Hopkins School of Medicine — Baltimore
• Medical University of South Carolina — Charleston
• University of South Carolina — Columbia

Публикации

• Bhogal SK, Teasell R, Speechley M. Intensity of aphasia therapy, impact on recovery. Stroke. 2003 Apr;34(4):987-93. doi: 10.1161/01.STR.0000062343.64383.D0. Epub 2003 Mar 20. PMID 12649521
• Brady MC, Kelly H, Godwin J, Enderby P, Campbell P. Speech and language therapy for aphasia following stroke. Cochrane Database Syst Rev. 2016 Jun 1;2016(6):CD000425. doi: 10.1002/14651858.CD000425.pub4. PMID 27245310
• 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. PMID 21216670
• FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2019 Jan 19;393(10168):265-274. doi: 10.1016/S0140-6736(18)32823-X. Epub 2018 Dec 5. PMID 30528472
• Doron R, Lotan D, Versano Z, Benatav L, Franko M, Armoza S, Kately N, Rehavi M. Escitalopram or novel herbal mixture treatments during or following exposure to stress reduce anxiety-like behavior through corticosterone and BDNF modifications. PLoS One. 2014 Apr 1;9(4):e91455. doi: 10.1371/journal.pone.0091455. eCollection 2014. PMID 24690945
• Enderby P, Broeckx J, Hospers W, Schildermans F, Deberdt W. Effect of piracetam on recovery and rehabilitation after stroke: a double-blind, placebo-controlled study. Clin Neuropharmacol. 1994 Aug;17(4):320-31. doi: 10.1097/00002826-199408000-00003. PMID 9316679
• Fridriksson J, Elm J, Stark BC, Basilakos A, Rorden C, Sen S, George MS, Gottfried M, Bonilha L. BDNF genotype and tDCS interaction in aphasia treatment. Brain Stimul. 2018 Nov-Dec;11(6):1276-1281. doi: 10.1016/j.brs.2018.08.009. Epub 2018 Aug 18. PMID 30150003
• Gu SC, Wang CD. Early Selective Serotonin Reuptake Inhibitors for Recovery after Stroke: A Meta-Analysis and Trial Sequential Analysis. J Stroke Cerebrovasc Dis. 2018 May;27(5):1178-1189. doi: 10.1016/j.jstrokecerebrovasdis.2017.11.031. Epub 2017 Dec 21. PMID 29276014

Идентификаторы

NCT: NCT03843463 · IRB00268564 · P50DC014664

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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