Escitalopram and Language Intervention for Subacute Aphasia

Stroke Clinical Trial

— ELISA  

Official title:

Escitalopram and Language Intervention for Subacute Aphasia (ELISA)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03843463
• Other study ID #: IRB00268564
• Secondary ID: P50DC014664
• Status: Recruiting
• Phase: Phase 2
• Start date: July 18, 2021
• Est. completion date: January 18, 2026

Study information

• Verified date: November 2023
• Source: Johns Hopkins University
• Contact: Argye Hillis-Trupe, MD
• Phone: (410) 614-2381
• Email: argye[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: January 18, 2026
• Est. primary completion date: September 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Aphasia
• Stroke

Intervention

Drug:
• Escitalopram 10mg
Escitalopram tablet
• Placebo
Sugar pill manufactured to mimic escitalopram 10 mg tablet

Behavioral:
• Computer-delivered naming treatment
15 45-minute sessions of computer-delivered naming treatment beginning two months following stroke

Locations

Country	Name	City	State
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of South Carolina	Columbia	South Carolina

Sponsors (5)

Lead Sponsor	Collaborator
Johns Hopkins University	Medical University of South Carolina, National Institute on Deafness and Other Communication Disorders (NIDCD), University of California, Irvine, University of South Carolina

Country where clinical trial is conducted

United States, 

References & Publications (26)

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. — View Citation

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. — View Citation

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. Erratum In: Lancet Neurol. 2011 Mar;10(3):205. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, Barbui C, Leucht S, Furukawa TA. Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015 Jul 15;180:179-84. doi: 10.1016/j.jad.2015.03.021. Epub 2015 Mar 31. — View Citation

Hillis AE, Beh YY, Sebastian R, Breining B, Tippett DC, Wright A, Saxena S, Rorden C, Bonilha L, Basilakos A, Yourganov G, Fridriksson J. Predicting recovery in acute poststroke aphasia. Ann Neurol. 2018 Mar;83(3):612-622. doi: 10.1002/ana.25184. Epub 2018 Mar 10. — View Citation

Hillis AE, Tippett DC. Stroke Recovery: Surprising Influences and Residual Consequences. Adv Med. 2014;2014:378263. doi: 10.1155/2014/378263. — View Citation

Hillis AE. The 'standard' for poststroke aphasia recovery. Stroke. 2010 Jul;41(7):1316-7. doi: 10.1161/STROKEAHA.110.585364. Epub 2010 Jun 10. No abstract available. — View Citation

Huber W, Willmes K, Poeck K, Van Vleymen B, Deberdt W. Piracetam as an adjuvant to language therapy for aphasia: a randomized double-blind placebo-controlled pilot study. Arch Phys Med Rehabil. 1997 Mar;78(3):245-50. doi: 10.1016/s0003-9993(97)90028-9. — View Citation

Jorge RE, Acion L, Moser D, Adams HP Jr, Robinson RG. Escitalopram and enhancement of cognitive recovery following stroke. Arch Gen Psychiatry. 2010 Feb;67(2):187-96. doi: 10.1001/archgenpsychiatry.2009.185. — View Citation

Kraglund KL, Mortensen JK, Damsbo AG, Modrau B, Simonsen SA, Iversen HK, Madsen M, Grove EL, Johnsen SP, Andersen G. Neuroregeneration and Vascular Protection by Citalopram in Acute Ischemic Stroke (TALOS). Stroke. 2018 Nov;49(11):2568-2576. doi: 10.1161/STROKEAHA.117.020067. — View Citation

Kurland J, Pulvermuller F, Silva N, Burke K, Andrianopoulos M. Constrained versus unconstrained intensive language therapy in two individuals with chronic, moderate-to-severe aphasia and apraxia of speech: behavioral and fMRI outcomes. Am J Speech Lang Pathol. 2012 May;21(2):S65-87. doi: 10.1044/1058-0360(2012/11-0113). Epub 2012 Jan 31. — View Citation

Lam RW. Antidepressants and QTc prolongation. J Psychiatry Neurosci. 2013 Mar;38(2):E5-6. doi: 10.1503/jpn.120256. No abstract available. — View Citation

Lazar RM, Minzer B, Antoniello D, Festa JR, Krakauer JW, Marshall RS. Improvement in aphasia scores after stroke is well predicted by initial severity. Stroke. 2010 Jul;41(7):1485-8. doi: 10.1161/STROKEAHA.109.577338. Epub 2010 Jun 10. — View Citation

Marangolo P, Fiori V, Sabatini U, De Pasquale G, Razzano C, Caltagirone C, Gili T. Bilateral Transcranial Direct Current Stimulation Language Treatment Enhances Functional Connectivity in the Left Hemisphere: Preliminary Data from Aphasia. J Cogn Neurosci. 2016 May;28(5):724-38. doi: 10.1162/jocn_a_00927. Epub 2016 Jan 25. — View Citation

Mead GE, Hsieh CF, Lee R, Kutlubaev MA, Claxton A, Hankey GJ, Hackett ML. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012 Nov 14;11(11):CD009286. doi: 10.1002/14651858.CD009286.pub2. — View Citation

Pan XL, Chen HF, Cheng X, Hu CC, Wang JW, Fu YM, Kong HM, Shao HJ. Effects of Paroxetine on Motor and Cognitive Function Recovery in Patients with Non-Depressed Ischemic Stroke: An Open Randomized Controlled Study. Brain Impairment. 2018 May:1-7.

Saeterdal I, Pike E, Ringerike T, Gjertsen MK. Efficacy and Safety for the Newer Antidepressants in Adults [Internet]. Oslo, Norway: Knowledge Centre for the Health Services at The Norwegian Institute of Public Health (NIPH); 2007 Jun. Report from Norwegian Knowledge Centre for the Health Services (NOKC) No. 17-2007. Available from http://www.ncbi.nlm.nih.gov/books/NBK464856/ — View Citation

Sanchez C, Reines EH, Montgomery SA. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? Int Clin Psychopharmacol. 2014 Jul;29(4):185-96. doi: 10.1097/YIC.0000000000000023. — View Citation

Sebastian R, Saxena S, Tsapkini K, Faria AV, Long C, Wright A, Davis C, Tippett DC, Mourdoukoutas AP, Bikson M, Celnik P, Hillis AE. Cerebellar tDCS: A Novel Approach to Augment Language Treatment Post-stroke. Front Hum Neurosci. 2017 Jan 12;10:695. doi: 10.3389/fnhum.2016.00695. eCollection 2016. — View Citation

Walker-Batson D, Curtis S, Natarajan R, Ford J, Dronkers N, Salmeron E, Lai J, Unwin DH. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke. 2001 Sep;32(9):2093-8. doi: 10.1161/hs0901.095720. — View Citation

Wang C, Zhang Y, Liu B, Long H, Yu C, Jiang T. Dosage effects of BDNF Val66Met polymorphism on cortical surface area and functional connectivity. J Neurosci. 2014 Feb 12;34(7):2645-51. doi: 10.1523/JNEUROSCI.3501-13.2014. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Philadelphia Naming Test short-form accuracy score	Number of correctly named items of 30 total items on the computerized picture naming assessment. Scores ranges from 0 to 30 with higher scores meaning better naming ability.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Language production as assessed by lexical features of discourse in "Cookie Theft" picture description	Lexical features, meaning carrying units of language (morphemes), will be counted for each Cookie Theft picture description. There is no maximum number of meaning carrying units, but norms are available to assist in the interpretation of this performance.	Baseline, 5 weeks after computer-delivered naming treatment
Secondary	Language production as assessed by content units included in picture description of "Cookie Theft"	Content units are based on a standard scoring template of commonly identified concepts (nouns and verbs) in the left and right regions of the "Cookie Theft" picture. Participants either include or fail to include 30 concepts on the left side of the picture and 23 concepts on the right side of the picture. A ratio of included left content units to included right content units then can be calculated and interpreted as a measure of hemispatial attention.	Baseline, 5 weeks after computer-delivered naming treatment
Secondary	Language production as assessed by rate of syllables per content unit produced in "Cookie Theft" picture description	Syllables included in the picture description are counted. Content units are based on a standard scoring template of commonly identified concepts (nouns and verbs) in the left and right regions of the "Cookie Theft" picture. Participants either include or fail to include 30 concepts on the left side of the picture and 23 concepts on the right side of the picture. The average rate of syllables per content unit produced can then be calculated and interpreted as a measure of efficiency in producing relevant information in the task.	Baseline, 5 weeks after computer-delivered naming treatment
Secondary	Depression as assessed by Patient Health Questionnaire (PHQ-9)	9 item scale scored 0-3 for each item. PHQ-9 scores of 5, 10, 15, and 20 represent mild, moderate, moderately severe, and severe depression. PHQ-9 >15 or suicidal ideation suggest depression sufficient for exclusion or removal from study.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Language production as assessed by Morphosyntactic Generation (MorGen) Test	60 item assessment of word morphology (e.g., plurals, possessives) and modifiers (e.g., number, size, color). Each item is scored based on produced accurate descriptors of an image relative to a second reference image (e.g., patients see two trees, one larger than the other, and the phrase "little tree" is elicited). Patients are scored for objects correctly named (nouns) out of 60, instances of correct use of plural marker out of 31, instances of correct use of numbers out of 8, instances of correct modifiers denoting size out of 16, instances of correct modifiers denoting color out of 19, instances of correct modifiers denoting possessive markers out of 17, and instances of correctly named possessing individuals (proper names provided on screen) out of 17. These scores can then be interpreted separately or averaged to interpret a broad morphosyntactic accuracy score.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Stroke severity as assessed by NIH Stroke Scale (NIHSS)	The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patient's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items.	Baseline, 5 weeks after computer-delivered naming treatment, 20 weeks after computer-delivered naming treatment
Secondary	Post-stroke level of disability as assessed by modified Rankin Scale (mRS)	The mRS is a 6-level scale from "0-No symptoms" to "6-dead" used to evaluate the degree of disability in patients who have suffered a stroke.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Stroke paresis severity as assessed by right hand strength	Right hand strength assessment by dynamometer	Baseline, 1 week after computer-delivered naming treatment
Secondary	Stroke paresis severity as assessed by right hand dexterity	Right hand dexterity assessment by 9 peg board test	Baseline, 1 week after computer-delivered naming treatment
Secondary	Change in new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella"	Change in new vocabulary items will be counted for each noun, verb, and adjective in the Cinderella retelling. There is no maximum measure of lexical diversity, but norms are available to assist in the interpretation of this performance.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Change in incidence of new vocabulary items as assessed by lexical diversity included in story retelling of "Cinderella"	Change in incidence of each new item will be counted for each noun, verb, and adjective in the Cinderella retelling. There is no maximum measure of lexical diversity, but norms are available to assist in the interpretation of this performance.	Baseline, 1 week after computer-delivered naming treatment
Secondary	Change in language production as assessed by speech errors produced during the story retelling of "Cinderella"	Change in number of errors will be counted after each retelling is recorded	Baseline, 1 week after computer-delivered naming treatment
Secondary	Change in Language production as assessed by speech pauses produced during the story retelling of "Cinderella"	Change in pauses will be counted after each retelling is recorded	Baseline, 1 week after computer-delivered naming treatment